Introduction: The COVID-19 pandemic has disrupted stroke care globally. This study aimed to assess the impact of COVID-19 on the clinical characteristics, acute treatment, and outcomes of patients with acute ischemic stroke (AIS) in Suzhou, China. Methods: This study retrospectively analyzed 506 hospitalized AIS patients from four stroke centers between December 10, 2022, and January 20, 2023. Patients were grouped by COVID- 19 infection status and timing. Clinical data and outcomes were compared with a pre-pandemic cohort from the SUMMITS-II Study. Results: Among included AIS patients, 54.3% were COVID-19-positive. Infected patients had higher baseline NIHSS scores, elevated inflammatory markers, and more in-hospital complications. Intravenous thrombolysis rates increased slightly during the pandemic, despite longer prehospital delays. Emotional disorders were more frequent post-stroke. COVID-19 infection, particularly concurrent with stroke onset, was linked to worse outcomes at 90 days and 1 year. Discussion: The findings suggest that the COVID-19 pandemic significantly influenced the clinical characteristics and outcomes of patients with acute ischemic stroke in Suzhou. Patients with AIS with concomitant COVID-19 infection presented with a higher prevalence of vascular risk factors and elevated inflammatory and coagulation markers. Moreover, COVID-19 infection occurring within one week of stroke onset was associated with more severe neurological deficits and poorer short- and long-term prognosis, highlighting the potential role of COVID-19 in worsening stroke outcomes. Conclusion: The COVID-19 pandemic adversely affected stroke severity and prognosis. While in-hospital workflows were preserved, delayed presentation and increased systemic burden contributed to unfavorable stroke outcomes. Strengthening stroke care delivery and psychological support during public health crises is essential.
Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, and the blood-brain barrier (BBB) restricts CNS delivery of macromolecular therapeutics such as antisense oligonucleotides (ASOs). Focused ultrasound (FUS) with microbubbles enables transient, noninvasive opening of the BBB for deliver SOD1-targeted ASOs. Methods: A narrative review of the literature in PubMed, Scopus, Web of Science, and Google Scholar (2020-2025) was conducted to evaluate FUS-assisted delivery of SOD1-targeted ASOs, with an emphasis on lipid- and calcium phosphate (CaP)- based nanoparticles. Results: Preclinical studies showed that FUS-mediated BBB opening (250 kHz; mechanical index 0.33; 30-s exposure; 0.15 mL/kg microbubbles) increased brain accumulation of nanoparticle- encapsulated ASOs by >3.5-fold compared with FUS without microbubbles. CaP lipid nanoparticles (~73 nm; -21 mV; 23-30% encapsulation efficiency) encapsulating tofersen demonstrated pH-responsive intracellular release. In wild-type and G93A SOD1 transgenic mice, FUS combined with CaP-ASO nanoparticles reduced SOD1 expression in sonicated cortical regions and increased lumbar spinal motor-neuron counts without detectable neuroinflammation or tissue damage. Discussion: Combining FUS-mediated BBB modulation with CaP nanoparticles provides a minimally invasive strategy for CNS ASO delivery. Observed spinal cord effects suggest wider CNS distribution, potentially involving CSF transport and retrograde axonal pathways. Clinical translation requires optimising FUS parameters, conducting long-term safety assessments, and managing skull acoustic variability. Conclusion: MRI-guided FUS combined with CaP lipid nanoparticles represents a promising non-invasive platform for SOD1-targeted ASO delivery and precision gene therapy in ALS.
Introduction: Huntington's Disease (HD) is an autosomal dominant neurodegenerative disorder that is caused by expansion of Cytosine-Adenine-Guanine (CAG) repeats in the Huntingtin (HTT) gene and leads to progressive motor, cognitive, and psychiatric dysfunction. Mitochondrial dysfunction is a major pathological feature of HD. Mitochondrial Rho GTPase 1 (Miro1) controls mitochondrial trafficking, calcium homeostasis, mitophagy, and neuronal signaling, and its dysregulation may contribute significantly to the progression of HD. Methods: The literature search to identify relevant studies on Miro1 biology, mitochondrial dysfunction, mitophagy, neuroinflammation, and emerging therapeutic strategies in HD followed a narrative review of the PubMed, Scopus, ScienceDirect, and Google Scholar databases. Original research articles, review articles, and preclinical studies published in English were screened for relevance, and the retrieved evidence was critically synthesized to provide an updated overview of Miro1's role in HD pathogenesis and its therapeutic potential. Results: Mutant Huntingtin (mHTT) perturbs Miro1-dependent mitochondrial transport, which leads to mitochondrial mislocalization, defective mitophagy, oxidative stress, and synaptic dysfunction. Miro1 dysregulation also facilitates neuroinflammatory signaling and neuronal vulnerability. Advances in AI have led to improved early diagnosis of HD through neuroimaging and digital biomarkers. Emerging therapies targeting Miro1, including gene therapy, nanocarriers, and pharmacological modulators, show promising neuroprotective potential in preclinical models. Discussion and Conclusion: Miro1 is a potentially important molecular link between mitochondrial dysfunction and neurodegeneration in HD. Targeting Miro1-mediated pathways may restore mitochondrial homeostasis and may be a promising therapeutic strategy for disease modification.
Abstract: Air pollution is an increasingly important public health concern in Pakistan, especially in rapidly urbanizing cities where concentrations of PM2.5, PM10, and other airborne toxicants frequently exceed recommended safety limits. Although the respiratory and cardiovascular consequences of air pollution are widely recognized, its contribution to neurovascular injury remains comparatively underrepresented in public health planning. This review synthesizes national and international evidence on the relationship between air pollution exposure and neurovascular outcomes, with particular emphasis on stroke-related mechanisms, cerebrovascular injury, and evidence gaps relevant to Pakistan and South Asia. Current evidence suggests that fine and ultrafine particulate matter may contribute to neurovascular damage through systemic inflammation, oxidative stress, endothelial dysfunction, blood–brain barrier disruption, microglial activation, vascular inflammation, atherosclerosis, and pro-thrombotic changes. These pathways provide biologically plausible links between chronic pollutant exposure and increased susceptibility to ischemic stroke, hemorrhagic stroke, cerebral small vessel disease, and impaired neurological recovery. However, Pakistan-specific longitudinal studies, biomarker-based investigations, and exposure-linked stroke surveillance data remain limited, restricting the integration of environmental exposure into neurovascular risk assessment and policy development. Given Pakistan’s high pollution burden, dense urban populations, and increasing stroke-related morbidity, air pollution should be considered a potentially modifiable neurovascular risk factor. Strengthening air-quality monitoring, developing local epidemiological cohorts, integrating pollution exposure with hospital and stroke-registry data, and implementing targeted prevention strategies for high-risk populations may help reduce the future burden of pollution-associated neurovascular disease in Pakistan.
Abstract: Neurodegenerative disorders such as Parkinson’s Disease (PD), Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), and Huntington’s Disease (HD) are characterized by progressive neuronal degeneration and severe therapeutic limitations due to the Blood–Brain Barrier (BBB). Recent advances in nanotechnology have enabled the development of nanoscale drug delivery systems capable of improving BBB penetration and enhancing therapeutic efficacy. This review discusses recent progress in Lipid Nanoparticles (LNPs), polymeric nanoparticles, exosomes, magnetic nanoparticles, gold nanoparticles, graphene quantum dots, and RNAloaded nanocarriers for brain-targeted delivery. Special emphasis is placed on receptor-mediated transcytosis, intranasal delivery, magnetic targeting, and ionizable lipid nanoparticle systems for nucleic acid delivery. Recent nanoformulations including curcumin-loaded nanoparticles, siRNA- loaded lipid nanoparticles, dopamine-loaded liposomes, and lactoferrin-functionalized polymeric nanoparticles are critically compared based on BBB penetration, therapeutic efficacy, toxicity, and translational potential. Furthermore, current clinical challenges including nanotoxicity, pharmacokinetics, large-scale manufacturing, and regulatory barriers are discussed. Nanotechnology- based therapeutics represent a promising strategy for improving diagnosis and treatment of neurodegenerative disorders and may facilitate the future development of precision nanomedicine.
