This study aimed to evaluate two intermittent fasting (IF) protocols (8:16 and 5:2) on sperm parameters and testicular microarchitecture in rats fed a high-fructose (HF) diet. Forty 12-week-old male Wistar albino rats were divided into four groups: Control, HF(20% fructose), (8:16)+HF (16-h daily fast), and (5:2)+HF(two fasting days/week). Following the 8-week treatment, biochemical, histological, and ultrastructural (TEM) analyses were performed.HF-diet led to significant weight gain and hyperglycemia. Both IF protocols effectively reduced body weight, while 8:16 IF significantly lowered glucose levels (p < .05). The control group showed significantly higher sperm counts and motility compared to the HF and 5:2 IF groups (p < .001). The 5:2 IF group showed the most severe degeneration, with significantly reduced Johnsen scores compared to both control and HF groups(p = .001).Histopathologically, the HF group exhibited deformed seminiferous tubules and basement membrane disorganization. Ultrastructural findings confirmed mitochondrial cristae loss, cytoplasmic vacuolization, and increased apoptosis in both IF groups, with the 5:2 protocol showing more pronounced heterochromatic nuclei and lipid droplet accumulation. While IF - particularly the 8:16 - effectively manages metabolic parameters like weight and glucose under HF diet conditions, it may exacerbate testicular damage and impair spermatogenesis. Specifically, the 5:2 IF protocol appears to have a more detrimental effect on sperm quality and testicular ultrastructure.
The future of organ-based therapies in monoclonal light chain-associated renal diseases is centered on the utilization of techniques that can identify specific targets to inhibit initiation and/or control progression. The present study of renal biopsies of patients with light chain deposition disease in different stages of glomerular involvement using spatial transcriptomics revealed unique gene expressions and activation of cellular pathways in mesangial cells responsible for the initiation and progression of the disease processes that can be targeted pharmacologically. Among the over-expressed genes were RPL41, RPS26, ACTA2-actin protein, TNC, and TGF (transforming growth factor) β1. The RPS and RPL genes regulate ribosomal function, their increase resulting in accentuated production of proteins. TGF-β drives matrix formation by mesangial cells, TNC is the gene responsible for the tenascin-rich mesangial nodules, and ACTA2 is an actin protein gene in myofibroblastic cells (phenotypically transformed mesangial cells), resulting in increased and cytoplasmic relocalization of actin in mesangial cells, leading to surface ruffling to promote interactions of monoclonal light chains with the SORL1 receptor. The pathways activated included the eukaryotic translation initiator, the extracellular matrix/proteoglycans and organization, and the TGF-β1 signaling, all aimed at increasing the extracellular matrix in the mesangium, responsible for its nodularity. The genes and cellular pathways differed in the various stages of glomerular LCDD, emphasizing the need for designing personalized therapies based on the evaluation of renal biopsies. Additional laboratory testing using existing models of LCDDs should be utilized to prove the efficacy of the proposed targeted interventions.
Primary renal neuroendocrine tumors (PRNETs) are exceptionally rare neoplasms that account for less than 1% of genitourinary neuroendocrine neoplasms and pose considerable diagnostic difficulty because of their non-specific clinicoradiological presentations and diverse histomorphology, which frequently mimics conventional renal epithelial tumors. We describe two adult patients with well-differentiated PRNET managed by partial nephrectomy including a 41-year-old male with a complex bosniak category IV cystic renal lesion, and another 43-year-old female with a tumor arising from the isthmus of a horse-shoe kidney. Both tumors showed organoid, trabecular, nested, tubulocystic, and focal cribriform architecture with low mitotic activity. Case 1 additionally showed focal capsular and perineural invasion despite of low-grade morphology. Tumor cells were diffusely positive for synaptophysin, chromogranin, and CD99, and negative for PAX8, CK7, CK20, WT1, TTF1, and CDX2, with a Ki-67 index below 2% in both. Electron microscopy confirmed dense-core neurosecretory granules, and both patients remain disease-free on radioimaging based follow-up. These cases illustrate that PRNET should be considered whenever a renal mass, including a complex cystic lesion or arising in a congenital anomalous kidney, not confirming thetypical epithelial morphology, and a combined histomorphological, immunohistochemical, and ultrastructural approach with prolonged surveillance is essential for accurate diagnosis and management.
This study investigated the effects of N-acetyl-seryl-aspartyl-lysyl-proline (AC-SDKP) treatment on the NLRP3 inflammasome complex and blood-spinal cord barrier (BSCB) permeability in a rat model of spinal cord injury (SCI). Male Wistar rats were divided into control, sham, and experimental groups, with the experimental group further divided into saline-treated and AC-SDKP-treated subgroups. SCI was induced using extradural clip compression, and AC-SDKP was administered intraperitoneally for 7 days post-injury. Spinal cord tissue samples were evaluated using light and electron microscopy, immunohistochemistry, and qRT-PCR. Biochemical analyses of IL-1β and IL-18 levels in blood and tissue samples were performed. Results showed that AC-SDKP treatment reduced edema, hemorrhage, and cavitation, and supported histological recovery. Immunohistochemistry revealed increased NeuN expression and decreased MMP-9 levels in the treatment group, indicating neuroprotection and reduced inflammation. AC-SDKP treatment also preserved BSCB integrity by increasing occludin, claudin-5, and VE-cadherin expression. Molecular analyses showed that AC-SDKP suppressed NF-κB activity and NLRP3 inflammasome levels, leading to decreased caspase-1, IL-1β, and IL-18 levels in both blood and spinal cord tissue. These findings suggest that AC-SDKP exerts neuroprotective effects by regulating inflammation at the cellular level and preserving BSCB integrity, making it a promising therapeutic agent for reducing secondary tissue damage and supporting recovery following SCI.
This study aimed to determine whether intrathecal administration of an interleukin-6 (IL-6) neutralizing antibody could reduce ultrastructural neuronal and vascular damage in a rat model of permanent middle cerebral artery occlusion (MCAO). Forty male Wistar rats were randomly assigned to four groups: Control, Sham-operated, Occlusion (MCAO + saline), and Treatment (MCAO + anti-rat IL-6 antibody). One week later, ischemic core brain tissue was processed for transmission electron microscopy to evaluate neuronal, axonal, and microvascular integrity. The Occlusion group showed severe ischemic injury, including mitochondrial swelling with cristolysis, cytoplasmic vacuolization, axonal edema, endothelial swelling, and perivascular astrocyte edema. By contrast, the Treatment group demonstrated marked ultrastructural preservation. Endothelial swelling and perivascular edema were reduced, neuronal nuclei were more preserved, and myelin sheath separation in white matter fibers was less pronounced than in the Occlusion group. Direct intrathecal IL-6 blockade was associated with qualitative cellular-level neuroprotection after permanent focal cerebral ischemia. The treatment attenuated inflammatory vascular injury and white matter damage, supporting IL-6 as a potential therapeutic target for limiting secondary stroke injury.
Acute kidney injury (AKI) is primarily caused by renal ischemia/reperfusion (I/R) injury, which is clinically linked to significant morbidity and death in both developed and developing countries. Therefore, the aim of this work is to compare the possible ameliorative effect of dapagliflozin (DAPA) versus human umbilical cord mesenchymal stem cells derived microvesicles (HUC-MSC-MVs) through biochemical, light, and electron microscope studies. Fifty-six adult male albino rats were divided into four groups: control, I/R, I/R+DAPA, and I/R+MVs groups. Both serum and tissue samples were collected for biochemical analysis. Renal specimens were processed to evaluate the histological structure, collagen content, desmin, and β-catenin immune expression. Morphometric and statistical analyses were performed. I/R group revealed prominent histoarchitectural alterations and a significant rise in the serum urea, creatinine, oxidative stress markers, and inflammatory mediators. Alterations were partially attenuated by DAPA therapy, whereas HUC-MSC-MVs significantly improved all parameters. We concluded that MSC-MVs administration exert a more significant ameliorative effect comparing to DAPA therapy via attenuating the oxidative stress and inflammation in addition to, restoring angiogenesis and cell proliferation. However, these findings remain preclinical and further researches are acclaimed for dose optimization, safety evaluation, and clinical validation before application in human AKI.
Podocyte infolding glomerulopathy (PIG) is a rare pathological diagnosis based on characteristic electron microscopic findings of microspheres and/or microtubular structures associated with podocyte infoldings into the glomerular basement membrane (GBM) and was proposed as a new entity from Japan in 2008. PIG has been increasingly reported not only in Japan but also worldwide; however, the precise cause and mechanisms of PIG are unknown. PIG cases investigated by repeated renal biopsies are even rarer. We herein report a patient with systemic lupus erythematosus (SLE) who showed progressive podocyte infoldings into GBM by serial renal biopsies and review previous reports of PIG comparing the findings of serial renal biopsies. PIG may progress in association with the activity of the underlying disease, particularly in patients with autoimmune diseases. In the present case, proteinuria persisted, and PIG progressed independently of the activity of SLE. Although PIG appears to follow a progressive course accompanied by proteinuria, further accumulation of data on PIG cases with serial renal biopsies will contribute to elucidating its pathophysiology.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that typically appears in early childhood, and there is a link between ASD and zinc deficiency. Neither the potential protective effects of the trace element zinc on the cerebellum against ultrastructural damage in animal models of ASD, nor its ability to protect against the modulation of the oxidative stress/gliosis/neuronal loss axis implicated in autism, have been previously investigated. Young rats were injected with the short-chain fatty acid produced by gut bacteria that is known to induce ASD, propionic acid (PPA) (500 mg/kg) for 5 days (model group) and the protection group was treated with 2 mg/kg zinc sulfate for two weeks following PPA injections. Cerebellum damage and behavioral impairment developed in the model group of rats as demonstrated by profound cerebellar ultrastructural alterations such as degeneration of Purkinje neurons and fragmented endoplasmic reticulum, as well as anxiety-like behavior and social interaction deficits. PPA also significantly (p < .05) modulated the cerebellar protein levels of the gliosis biomarker GFAP and the neuronal loss biomarker calbindin D28K, as well as the cerebellar tissue levels of zinc, glutathione, and the oxidative stress biomarker malondialdehyde (MDA). All these parameters were significantly (p < .05) protected by zinc treatment. Additionally, we observed a significant (p < .001) correlation between the degree of Purkinje cell damage and these parameters associated with autism. In conclusion, PPA-induced autistic behaviors in rats are associated with alteration to the cerebellar ultrastructure, modulation of the oxidative stress/gliosis/neuronal loss axis of ASD, and a decline in zinc and glutathione, which were protected by zinc treatment.
Adult neural stem cells (NSCs) are located in the sub-granular zone (SGZ) of the dentate gyrus (DG) of the hippocampus, one of the prominent regions of neurogenesis in the adult brain. Activation of endogenous stem cells may provide a therapeutic approach in demyelinating diseases. Due to their minuscule size, nanoparticles (AuNPs) can cross the blood-brain barrier. To evaluate the effect of AuNPs on adult NSCs and the progression of demyelination in the hippocampus in a model of demyelination, thirty-two adult mice were divided into: control group I, AuNPs group II (10 mg/kg BW/day), cuprizone (CPZ) group III (0.2% orally for 8 weeks to induce demyelination), and CPZ & AuNPs group IV. Hippocampus was prepared for light microscopy, nestin immunohistochemical staining (NSCs' immune marker), and electron microscopy. In groups I and II, spindle-shaped adult NSCs in the SGZ of DG showed a positive nestin immunoreaction. In group III, most of the nerves were demyelinated. Pyramidal and granular neurons showed degenerative changes. Nestin-immune-positive cells were significantly decreased. In group IV, preservation of the myelin, less degenerative changes, and a significant increase in nestin-positive cells were detected. In conclusion, AuNPs activated adult NSCs in the mouse hippocampus, partially ameliorated degenerative changes, and enhanced partial remyelination in the CPZ demyelination model.
Autism is a neurodevelopmental condition with challenges in establishing and sustaining social relationships and communication. Apigenin (AP) is a natural flavonoid with numerous valuable effects on brain disorders. The current study emerged to study the cerebellar histopathological changes in valproic acid (VPA)-induced autism in male albino rat pups and assess the possible neuroprotective role of AP in minimizing these alterations. Forty male albino rat pups were categorized randomly into four equal groups: control group, AP group administered AP (250 mg/kg/day orally) from postnatal days (PND)14 to PND 40, VPA group received single subcutaneous injection of VPA (400 mg/kg) on PND14 and VPA+AP group were injected with VPA, then received AP at the identical dosage and approach as the preceding groups. Shrunken Purkinje cells with dark heterochromatic nuclei, neuropil vacuolation, and myelin sheath deformities were reported on VPA administration. A significant rise in cerebellar immune expression of GFAP, p-Tau and nestin. Also, a significant reduction in the duration of sniffing, line crossing, and rearing was recorded. Additionally, a decline of glutathione peroxidase, serotonin and the rise of malondialdehyde and IL-1β levels were recorded in cerebellar homogenate. The co-treatment of AP with VPA significantly rescued these histological alterations and reinstated antioxidant equilibrium.
BACKGROUND:C3 glomerulopathy (C3G) is a rare type of glomerular disease characterized by predominant deposits of C3 complement. Although dominant C3 immunofluorescent (IF) staining has become well known as a diagnostic criterion, the findings of electron microscopy (EM) are not well specified. The goal of this study was to scrutinize the characteristic features of C3 deposits on EM and to correlate with C3 IF staining patterns. METHODS:We examined the EM images of a cohort of 24 cases of C3G (22 C3 dominant glomerulonephritis [C3GN] and 2 dense deposit disease [DDD]) to determine their characteristic features when compared to a cohort of patients with immune complex-mediated glomerulonephritis. RESULTS:In our patients with C3G, the C3 deposits were present in all three glomerular compartments (mesangial, subendothelial, and subepithelial spaces) and they had the following features: (1) Smear pattern of C3 deposits along glomerular basement membranes (GBM) and subepithelial spaces; (2) C3 deposits were mostly lighter in gray colors as opposed to the dark black appearance of immune complex deposits (ICD); (3) C3 aggregates revealed smooth contours with a homogeneous fine granular appearance when compared to the humpy and bumpy appearance of ICD, and (4) C3 deposits rarely showed either retraction artifacts around the deposits or vacuolization within the GBM or mesangial areas. CONCLUSIONS:In our cohort, C3 deposits exhibit reproducible EM features that are well correlated with clinical data and dominant C3 staining by IF and are different from ICD upon securitized review.
Lung fibrosis is an irreversible life-threatening condition. So, this study directed to investigate the structure of lung tissue following bleomycin-induced pulmonary injury and to evaluate the potential protective effects of pirfenidone, granulocyte colony-stimulating factor (GCSF), and their combined administration. Fifty-six adult rats were allocated into control, bleomycin-treated, pirfenidone-treated, GCSF-treated, and combination groups. Lung specimens were processed and examined using light & transmission electron microscopes beside biochemical examination for MDA and GSH. Bleomycin administration caused marked structural alterations. Both Pirfenidone and GCSF alone resulted in partial improvement of pneumocyte ultrastructure and reduced fibrotic features. Notably, the combined therapy group demonstrated the most evident protection, with near-normal pneumocyte morphology and reduced degenerative changes. These findings suggest that combined pirfenidone and GCSF therapy exerts a synergistic effect in ameliorating bleomycin-induced lung injury at the ultrastructural level.
Differentiated human SH-SY5Y neuroblastoma cells used to model neurodegenerative defects, cholinergic neuron differentiation, neurotropic virus infection, and neurotoxicity have not been comprehensively studied with fine structure. Our goal is thus to further disclose their cytology. Differentiated in vitro with retinoic acid (RA), SH-SY5Y cells were processed for fine structure analyses with transmission, scanning electron microscopy, and X-ray spectroscopy microanalysis. The neoplastic cells showed typical high nucleus: cytoplasm ratio with neuron-like profiles extending to one long neurite that can carry dense core vesicles and associated cytoskeletons. Among the organelles, one-fifth of mitochondria profiles were noted to bear prominent anomalies of both outer and internal membranes. These organelles formed bursts, long or folded lamellae, with the matrix either replaced by accumulated contrasted compound or striated content created through random sectioning sorts of appendages constituting views of so-called "lamellar bodies," and other dense bodies accompanied by mitophagy. Most lining membranes joined the endoplasmic reticulum network with lipid storage droplets. RA differentiation of neuroblastoma cells involved cell genome and mitochondria metabolism to favor an increased lipid and phospholipids precursors to store associated endoplasm and mitochondria membrane and matrix changes resulting in defective fine structures and content. Some of them bore analogy with those noted when one or more mitochondria regulatory proteins (e.g. OPA1 and mitofusin) occurred in other neurodegenerative pathologies, including Parkinson's disease. Our observations should incite further molecular investigations about this neuroblastoma cell proteome and lipidome organelles because of this cell line usage in numerous biomedical investigations.
Renal tubular casts are cylindrical structures formed primarily in the distal convoluted tubule or collecting tubule. They are composed of materials filling the tubular lumen and molding along its contour. The clinicopathologic attributes of tubular cast including light microscopic features are well described. In contrast, knowledge on the ultrastructural changes of these casts is limited. This communication focuses on the electron microscopic studies of renal tubular casts. It fully abstracts the current literature and, together with a meticulous review of institutional renal biopsy archive, confirms the current knowledge, expands it, and further reports novel observations. Distinctive and rarely pathognomonic ultrastructural features are expressed by most types of tubular casts, which are well correlated with light microscopic changes. This review further demonstrates that beyond the often elegant and artful images under the electron microscope, the ultrastructural morphology of the tubular casts not only offers diagnostic clue or initiate molecular/chemical studies, but can also provide definite diagnosis or pathogenetic insight unaffordable by other traditional studies.
Lutein provides a promising approach to protect the testes against damage induced by deltamethrin. The current study was applied to investigate the protective effect of lutein on the testis of adult male albino rats against testicular toxicity induced by deltamethrin. Sixty adult male albino rats were randomly allocated into six experimental groups. Group I served as control, group II received lutein (40 mg/kg/day orally), group III received deltamethrin (5 mg/kg/day orally), group IV received deltamethrin (5 mg/kg/day orally) concomitant with lutein (40 mg/kg/day orally), all for 4 weeks. Group V received lutein (40 mg/kg/day) throughout 8 weeks, whereas deltamethrin was given at week 5 till the end of week 8. Group VI served as a withdrawal group in which animals received deltamethrin for four weeks, followed by a four-week treatment-free period to assess the reversibility of its toxic effects. Biochemical, histological, and ultrastructural techniques were used to evaluate the testicular changes. Deltamethrin-treated rats showed decreased serum testosterone. Testicular tissue exhibited pronounced histopathological changes. Histopathological examination of testicular tissue showed that apoptosis was observed in the basal germ cells, primary and secondary spermatocytes. The testes exhibited distorted Sertoli cells accompanied by depletion of spermatogenic cells, along with significant reductions in seminiferous tubular diameter and serum testosterone levels relative to control. While the percentage of apoptotic cells was significantly increased. Group V showed improvement in histological structure, the testosterone levels, and other morphometrical parameters. Pretreatment of lutein to deltamethrin-treated rats prevents the histopathological alterations by deltamethrin in testis.
In 2018, the FDA issued an alert about a potential link between dilated cardiomyopathy (DCM) in pet dogs and cats and diets high in pulses (peas, lentils, chickpeas, and beans). Given reported myocardial ultrastructural abnormalities in this disease, the objective was to compare myocardial mitochondria, autophagic structures, and other subcellular organelles in cats with DCM eating high- versus low-pulse diets. Left ventricular tissue from cats with DCM eating high- (n = 4) or low-pulse (n = 3) diets was evaluated using transmission electron microscopy. Myofibrils, mitochondria, T-tubules, nuclei, z-lines, autophagic structures, and intercalated discs were evaluated qualitatively. Diet groups were compared for qualitative findings, as well as mitochondrial number, area, and perimeter; sarcomere length; lipid droplet number and area, and mitochondrial stage in the perinuclear, interfibrillar, and subsarcolemmal regions. Cats with DCM eating high-pulse diets had more unknown vacuoles and fewer Stage B mitochondria, with more Stage BC mitochondria compared to cats with DCM eating low-pulse diets. These results suggest that cats with DCM eating high-pulse diets have mitochondria in more advanced stages of degeneration. The higher number of unknown vacuoles could represent more mitochondrial degeneration or increased autophagy. Further ultrastructural investigation is warranted to help identify the cause of this diet-associated disease.
Lung fibrosis is defined as fibrotic change of the lung architecture within 2.5-3 years of diagnosis, ultimately leading to respiratory failure and death. Prolonged exposure to high concentrations of carbon tetrachloride, especially vapor, can cause lung destruction. Autophagy was crucial for maintaining the organs' homeostasis. Deficit in autophagy has been commonly associated with fibrosis and pneumonia. Recent research suggests that metformin may provide protection against a variety of lung ailments. To investigate how metformin protects against lung damage caused by carbon tetrachloride via the autophagy pathway, 30 adult male albino rats (10 rats each) were divided into three equal groups. One group served as the control. Group 2: received CCl4 1.5 mg/kg twice weekly S.C. for a duration of 12 weeks. Group 3: Oral metformin and CCl4 were administered for 12 weeks at a dose of 100 mg/kg/day and 1.5 mg/kg twice weekly S.C. After the animal died, its lungs were taken out of each group and studied under an electron and light microscope in addition to being used for immunological research. The histological abnormalities in the lung tissue caused by the administration of CCl4 included areas of tissue destruction, congestion, and fibrosis. Pneumocyte type I, type II, and collagen fiber deposition were found to have changed ultrastructurally. Concurrent metformin and CCl4 treatment resulted in improvements. The histological and biochemical effects of CCl4 on lung tissue can be modulated by administration of metformin.
Simvastatin is antihyperlipidemic drugs that inhibit hydroxy methylglutaryl CoA reductase to decrease cholesterol synthesis; however, it causes skeletal myopathy. Omega-3 are polyunsaturated fatty acids with anti-inflammatory and anti-oxidant effects. Mast cells have an important role in the response to tissue injury by secreting different mediators and cytokines. The current study was performed to assess the role of mast cells in simvastatin-induced myopathy and the possible protective role of omega-3 fatty acids. Forty adult male albino rats were divided into four main groups received the drugs orally for of 21 days. Group 1: 1 ml distilled water, group 2: 300 mg/kg/day omega-3, group 3: 88 mg/kg/day simvastatin, and group 4: 88 mg/kg/day simvastatin plus 300 mg/kg/day omega-3. Light and electron microscopic studies were done along with morphometric and statistical studies. Group 1 and 2 showed regular histological structure. By light microscope, group 3 revealed muscle fiber disorganization, splitting, loss of striations, and cytoplasmic fragmentation. Some nuclei were centrally displaced. Toluidine blue sections showed a large number of mast cells. By transmission electron microscope, there was loss of the regular banding pattern with irregular mitochondria, nuclei, and sarcolemma. The concurrent administration of simvastatin with omega-3 showed less myopathic changes, decrease in mast cell numbers and more activation of the satellite stem cells to accomplish the process of muscle regeneration. In conclusion, the administration of omega-3 can decrease the myopathic changes of simvastatin. Further studies are recommended to explore the mast cells' role in the progression and repair of statin-induced myopathy.
Intestinal ischemia-reperfusion injury (IIRI) is a life-threatening vascular emergency with high mortality, commonly occurring as a complication of hemorrhagic shock or acute mesenteric arterial occlusion. When revascularization is performed after this issue, injury will occur. The influence of MSC-MVs and G-CSF on IIRI was detected in this study. Fifty-six male adult albino rats were allocated into five groups: control, ischemia-reperfusion, MSC-MVs, G-CSF, and recovery. Ischemic injury was induced for one hour using micro-vascular clamp across the superior mesenteric artery at its beginning from the aorta. After that, the clamp was withdrawn to allow reperfusion for two hours. At the end of experimental period, rats were sacrificed. Jejunal tissues were processed for assessment of oxidative stress markers (MDA and SOD) as well as for histological and immune histo-chemical analysis. Ischemia-reperfusion group revealed highly statistically significant increase in tissue MDA while SOD showed the reverse, histologically by light microscopic examination; inflammatory cellular infiltration, congested blood vessels, and separated muscle fibers in muscularis mucosa were observed. Ultrastructurally, absorptive columnar cells appeared with heterochromatic nuclei, lost apical microvilli, and widen intercellular space. These findings showed more improvement in MSC-MVs group in comparison with G-CSF group while recovery group exhibited severe affection.
Neurodegeneration (ND) is a major medical problem in elderly. Olfactory bulb represents an early-vulnerable brain area to ND. Mesenchymal stem cells-derived exosomes are currently evaluated as a possible therapeutic agent for several diseases. This study aimed to assess exosomes-therapeutic potential on ND-induced olfactory bulb changes. Forty-five adult male albino rats were equally categorized into three groups: control (I), ND (II), and exosomes treated (III). ND was induced in groups II and III using aluminum chloride, then group III rats received a single intravenous injection of 200 µg exosomes. Buried food test was conducted to assess sense of olfaction. Blood was collected to assess serum malondialdehyde (MDA) and total antioxidant capacity (TAC) levels. Olfactory bulb specimens were prepared for histological and immunohistochemical (GFAP & synaptophysin) studies. ND group displayed a highly significant increase in buried food test time and MDA level, along with decrease in TAC level. Marked histological changes were observed affecting nerve cells, synapses, neuropil and bulb vasculature with a highly significant increase in GFAP area percentage and decrease in that of synaptophysin. Treatment with exosomes in group III markedly ameliorated these changes. These results reflected that MSCs-derived exosomes had a remarkable therapeutic potential against ND-induced changes in olfactory bulb.
