Repeated concussion traumatic brain injury (TBI) results in long-term brain damage and cognitive dysfunctions, leading to neurodegenerative diseases. The brain clearance system plays a crucial role in TBI recovery and neurodegenerative disease amelioration by draining waste macromolecules from the brain. Pharmacological therapeutics have failed to demonstrate benefits in human TBI. Photobiomodulation (PBM) has gained interest in neuroscience and has been shown to improve brain drainage. Here, we evaluated the efficiency of PBM in the treatment of multiple concussions in mice and the augmentation of the brain clearance system. Three consecutive closed-head concussive TBIs were induced with a 1-h interval to the left hemisphere in C57BL/6 male mice. A near-infrared irradiation (1270 nm, 10 mW/cm2) was used for PBM 4 h after the last TBI and the following 3 days twice a day. Laser speckle contrast imaging was used to assess cerebral blood flow (rCBF). In vivo 2-photon laser scanning microscopy assessed PBM effects on cerebral microcirculation, tissue oxygen supply (NADH), and meningeal lymphatics clearance. Brain compliance was evaluated by intracranial pressure waveform analysis. Neurological severity scores were obtained at 0–3 days after TBI. Two-way ANOVA for multiple comparisons was used to test intergroup differences, with the statistical significance set at p < 0.05. Multiple concussions progressively impaired rCBF, cortical microcirculation, tissue oxygen supply, and brain drainage function (p < 0.05). Compared to the sham-treated group, PBM improved rCBF, microcirculation, tissue oxygenation, and the brain drainage system (p < 0.05). Neurological function was more preserved in the PBMT group than in sham-treated mice (p < 0.05). Our study demonstrated that PBMT can be used as an adjunct therapy even in the acute period of TBI.

This retrospective study aimed to evaluate the dynamics of cerebral edema, quantified by net water uptake (NWU), in relation to endovascular thrombectomy (EVT) outcomes using the extended Thrombolysis in Cerebral Infarction (eTICI) scale and treatment results in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). 93 patients (44 men, 49 women; median age 68.7 years) underwent EVT within 6 h of AIS onset, with NWU calculated from non-contrast CT based on perfusion CT data using the formula: NWU = (1 − Dischemia/Dnormal) × 100

A functional blood-brain barrier (BBB) is essential for the central nervous system (CNS) homeostasis and its disruption is an early event in acute brain injury and chronic neurodegeneration. Hypoxia triggers BBB breakdown, promoting endothelial dysfunction, oxidative stress, metabolic dysregulation and thrombo-inflammatory responses that compromise barrier integrity. However, strategies that directly restore BBB function remain limited. Here, we investigated whether photobiomodulation (PBM), a non-invasive light therapy, can rescue BBB dysfunction following acute hypoxic stress. Using a multicellular in vitro BBB model comprising immortalised human brain microvascular endothelial cells, pericytes and astrocytes, we induced hypoxic injury (6 h, 1% O₂) and applied three PBM treatments during recovery. Hypoxia significantly reduced transendothelial electrical resistance (TEER), whereas PBM restored barrier function in endothelial monocultures and tri-cultures. Endothelial cells showed the strongest hypoxic response, with increased hypoxia-inducible factor-1α, plasminogen activator inhibitor-1 and von Willebrand factor (vWF), all attenuated by PBM. Importantly, siRNA-mediated knockdown of vWF partially recapitulated PBM-induced barrier rescue, identifying endothelial vWF as a mediator of recovery. PBM also reduced reactive oxygen species in hypoxic astrocytes and pericytes, indicating coordinated multicellular modulation. These findings demonstrate that PBM restores BBB integrity after hypoxic insult by modulating endothelial thrombo-inflammatory signalling while reducing oxidative stress in glial cells. Rather than acting as a general cytoprotective stimulus, PBM engages defined molecular pathways linked to endothelial activation. This work establishes a mechanistically informed platform for studying BBB repair and supports PBM as a targeted strategy to protect vascular integrity in hypoxia-associated neurological disorders. Hypoxia is a major driver of blood-brain barrier (BBB) dysfunction, yet there are currently no targeted therapies that directly restore barrier integrity. Photobiomodulation (PBM) is a non-invasive low-level light intervention known to facilitate mitochondrial function and cellular stress responses. In a human in vitro BBB model, repeated PBM treatment restored transendothelial electrical resistance (TEER) 24 and 48 hours after hypoxic injury, with endothelial rescue linked to downregulation of von Willebrand factor (vWF). PBM modulated oxidative stress, hypoxia signalling, and thrombo-inflammatory pathways across endothelial cells, astrocytes, and pericytes. These findings support light-driven modulation of endothelial signalling as a potential strategy to restore BBB integrity in hypoxia-associated neurological conditions.

Traumatic brain injury (TBI) induces microvascular dysfunction, tissue hypoxia, and blood–brain barrier (BBB) breakdown, driving secondary injury. High-frequency pulsed electromagnetic field (PEMF) stimulation is an emerging noninvasive “electroceutical” therapy that we have previously shown increases cerebral blood flow (CBF) and tissue oxygenation in the healthy rat brain. Here, we investigated whether acute PEMF could mitigate microvascular pathology in a rat TBI model. Male Sprague–Dawley rats underwent moderate fluid percussion injury (FPI) over the parietal cortex. Using in vivo two-photon laser scanning microscopy (2PLSM), we quantified peri-contusional arteriolar diameter, capillary red blood cell (RBC) velocity, microvascular shunt (MVS) flow, tissue oxygenation (NADH autofluorescence), and BBB permeability before and after a single 30-min PEMF (27.12 MHz, 3-ms bursts at 5 Hz, 6 V/m) or sham treatment. PEMF applied 1 h post-TBI significantly reversed pathological MVS flow (MVS/capillary ratio: 0.69 ± 0.06 vs. sham 0.90 ± 0.08, p < 0.01), increased capillary RBC velocity (86.3 ± 10.1

Severe traumatic brain injury (sTBI) disrupts cerebral hemodynamics, yet the biomechanical consequences on arterial wall shear stress (WSS) remain poorly understood. The aim was to assess the changes in wall shear stress in the middle cerebral artery (WSSmca) in severe traumatic brain injury (sTBI) patients with and without the development of intracranial hematomas (ICH). A total of 78 patients with sTBI (mean age 35.1 ± 7.3 years, 40 men, 38 women) were enrolled. Group 1 included 39 patients without ICH, and Group 2 included 39 patients after surgical removal of peradural (epidural or subdural) ICH. Computed tomography and transcranial Doppler were performed 2–5 days after TBI. WSSmca was calculated using the Hagen–Poiseuille’s equation. Statistical analysis was performed using the T-Student’s test to compare WSSmca between the ICH-ipsilateral and ICH-contralateral hemispheres. Data are presented as mean ± SD, with significance set at p < 0.05. Wall shear stress in M1 segments of MCAs significantly exceeded the reference range (3.64 ± 1.25 Pa) in both groups (p < 0.05). In Group 1, mean WSSmca was 4.27 ± 0.23 Pa. In Group 2, WSSmca was significantly higher on the ipsilateral side (6.29 ± 0.47 Pa) and contralateral side (5.38 ± 0.61 Pa) compared to Group 1 (p < 0.001). Ipsilateral previously removed ICH WSSmca in Group 2 was also significantly higher than contralateral WSSmca (p = 0.008). Elevated WSS persists after ICH evacuation, suggesting sustained biomechanical stress on arterial walls. These findings highlight shear-mediated contributions to secondary cerebrovascular injury in sTBI and warrant further biophysical investigation.

Individuals experiencing severe polytrauma are typically transported to the highest level of care as soon as possible, including helicopter evacuation from remote and/or rural environments. However, several recent preclinical and clinical studies have suggested that aeromedical evacuation exacerbates central nervous system injury and inflammation, and potentially results in increased mortality, questioning the right time and conditions under which to fly. Twenty-four swine with moderate-to-severe rotational traumatic brain injury (TBI) and ∼40% blood loss were randomly assigned to standard (∼8500 feet), tactical (evasive maneuvering), or mock (stationary on ground) helicopter (U.S. Army Black Hawk; HH-60M model) evacuation 2 h post-injury, with standard recommended therapies initiated in-flight. Results indicated that tactical evacuation was associated with increased cerebral perfusion pressure and inflammation (IL-6) post-flight relative to the standard and mock evacuation profiles, even after statistically controlling for pre-flight trauma procedures. Although the overall mortality rate was ∼25%, indicating severe polytrauma, no differences in mortality were observed as a function of aeromedical evacuation scenarios. Primary biomarkers of hemorrhagic shock, traumatic brain injury, lung and kidney pathology were also negative for aeromedical evacuation effects. In summary, the medical benefits associated with immediate (i.e., within a few hours of injury) helicopter evacuation of severe polytrauma patients likely outweigh the few increased complications associated with flight, as the latter may only be present during more extreme helicopter evacuation scenarios. Additional studies are needed to address potential adjunctive therapies that can be administered pre-flight to minimize the potential adverse effects of tactical flight.

The aim of our study was to compare brain tissue net water uptake (NWU), cerebral oxygenation, and microcirculation changes in perilesional penumbra foci (PPF) in moderate isolated traumatic brain injury (moiTBI) patients. Materials and Methods: 77 moiTBI patients (women 35; men 42, age 37 years [34;39]) with unilateral frontal/frontotemporal lesions (Marshall II-III) were included in this retrospective, non-randomized, single-center study. Perfusion parameters were measured in PPF zones and determined using multiphase perfusion computed tomography (PCT) in the first 2 days after trauma and admission. NWU in hypoattenuated perilesional zones was calculated using non-contrast CT. Cerebral oxygenation (SctO2) was simultaneously measured using near-infrared spectroscopy in the frontal lobes with PCT. Data are shown as a median [interquartile range]. Statistical analysis was performed using nonparametric statistics. P < 0.05 was considered statistically significant. Results: In PPF, SctO2 was 64.03

Current treatments for ischemic stroke are not focused on microvascular cerebral blood flow (mvCBF), which actually delivers oxygen to tissue and is significantly impaired during a stroke. We previously showed that drag-reducing polymers (DRPs, 2 μg/ml), injected just after permanent middle cerebral artery occlusion (pMCAO) in rats, effectively restored mvCBF and tissue oxygenation. The aim of this work was to assess the efficiency of DRPs administered at various time points post-onset. DRPs (2 μg/ml) or saline was i.v. injected 0.5, 3, or 6 h after pMCAO induction in rats (n = 10/group). Laser speckle contrast imaging (LSCI) was used to evaluate regional cerebral blood flow in the parietal cortex and estimate the ischemic area. In vivo 2-photon laser scanning microscopy (2PLSM) was used to assess the effects on mvCBF and tissue hypoxia (NADH). Two-way ANOVA for multiple comparisons was used to test intergroup differences with the statistical significance level set at p < 0.05. PMCAO progressively decreased cortical mvCBF, causing tissue hypoxia (p < 0.05). Intravenous administration of DRPs at 0.5, 3, and 6 h post-pMCAO effectively improved cerebral microcirculation and oxygen delivery to tissue in a time-dependent manner compared to the saline-treated group (p < 0.05). DRPs efficacy reduced with the time of application from 0.5 to 6 h after pMCAO but remained significant compared to the saline-treated group (p < 0.05). DRPs augment collateral microcirculatory flow through leptomeningeal and pial anastomoses that interconnect the middle, anterior, and posterior cerebral artery watershed territories. We demonstrated that DRPs can be used as a new effective adjunct therapy for ischemic stroke, even without reperfusion and after delayed administration following the stroke onset.

Background:Post-traumatic cerebral vasospasm (CVS) significantly worsens outcomes in moderate-to-severe traumatic brain injury (msTBI). While wall shear stress (WSS) modulates endothelial function, its state in post-traumatic CVS remains poorly understood. We aimed to assess supraclinoid internal carotid artery (ICA) WSS in msTBI patients with and without non-surgical parenchymal hemorrhage. Methods:This retrospective cohort study (2013-2024) included 85 adults with msTBI and angiographic CVS. Patients were divided into Group 1 (Marshall II-III, no hematoma; n=43) and Group 2 (Marshall IV, non-surgical parenchymal hemorrhage; n=42). Dynamic helical CT angiography (DHCTA) and Doppler ultrasound were performed 2-5 days post-injury. WSS in the ICA C7 segment was calculated using a Poiseuille-based formula incorporating mean CBFV and vessel radius. Results:ICA WSS significantly exceeded the reference range (0.82 ± 0.08 Pa) in both groups (p<0.001). In Group 2, WSS was significantly higher than in Group 1 (p<0.0001). Specifically, Group 2 ipsilateral WSS (64.4 ± 9.8 Pa) was significantly higher than both the contralateral side (49.3 ± 8.3 Pa; p=0.021) and the Group 1 mean (33.2 ± 7.5 Pa; p<0.0001). No significant age-WSS correlation was observed (p=0.72). Group 2 exhibited a trend toward worse clinical outcomes (GOS), though only moderate disability (GOS 4) showed a significant difference (p<0.05). Conclusions:Post-traumatic CVS in msTBI is associated with markedly elevated ICA WSS. The presence of parenchymal hemorrhage further amplifies this hemodynamic stress, potentially contributing to non-physiological microcirculatory remodeling. These findings suggest WSS could serve as a biomarker for secondary brain injury risk, necessitating individualized surgical and medical management.

Background:Decompressive craniectomy (DC) is used to treat refractory intracranial hypertension after pediatric severe traumatic brain injury (sTBI), but early postoperative neurosurgical complications and their predictors-particularly intracranial pressure (ICP) burden-remain inconsistently characterized. Methods:We performed a retrospective cohort study of consecutive pediatric patients (<18 years) with sTBI (Glasgow Coma Scale [GCS] 3-8) who underwent DC at a single high-volume trauma center. Early postoperative neurosurgical complications were defined a priori as events occurring within 7 days after DC or before hospital discharge: secondary intracranial hemorrhage, central nervous system (CNS) infection, wound dehiscence, and cerebrospinal fluid (CSF) leak. Associations with injury severity, imaging, and ICP variables (mean intraoperative ICP; cumulative duration of ICP >20 mmHg before DC) were evaluated. Results:Eighty-three children were included. At least one early neurosurgical complication occurred in 33 of 83 patients (39.8%). Secondary intracranial hemorrhage occurred in 29/83 (34.9%), CNS infection in 7/83 (8.4%), wound dehiscence in 6/83 (7.2%), and CSF leak in 4/83 (4.8%). Patients with complications had significantly higher intraoperative ICP (40.5 ± 13.5 vs 28.6 ± 4.3 mmHg; p = 0.0058) and longer pre-DC duration of ICP >20 mmHg (4.1 ± 5.9 vs 1.6 ± 2.5 hours; p = 0.0296). At 6 months, 25/83 (30.1%) had died; among survivors, 28/58 (48.3%) achieved a favorable outcome (GOS 4-5), 12% in 1 group (without complications). Conclusions:Early postoperative complications after pediatric DC were common and predominantly hemorrhagic. A greater ICP burden before and during DC was associated with these events. The co-occurrence of CSF leak and CNS infection highlights the importance of dural closure strategies that minimize CSF egress and the need for vigilant postoperative surveillance.

Background: Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Beyond its systemic effects, hypertension elevates intracranial pressure (ICP) and alters the ICP waveform morphology — specifically increasing the P2/P1 ratio, which indicates reduced intracranial compliance (ICC). The intracranial baroreflex normally triggers pressor responses to maintain cerebral perfusion pressure (CPP) during increases in ICP. However, whether this reflex is impaired in chronic hypertension remains unclear. We tested the hypothesis that 2-kidney, 1-clip (2K1C) hypertensive rats exhibit impaired intracranial baroreflex responses to increased intracranial volume. Methods: Male Holtzman rats underwent 2K1C renovascular hypertension or sham surgery (normotensive, NT). Six weeks later, under urethane anesthesia, ICP (via an invasive sensor), mean arterial pressure (MAP), and heart rate were recorded. Two protocols were performed: (1) a bolus intracerebroventricular (ICV) infusion of 30 µL of artificial cerebrospinal fluid (aCSF) at 100 µL/min; and (2) a continuous ICV infusion of 100 µL of aCSF at 10 µL/min over 10 min. ICC was calculated from the P2/P1 ratio and the volume-pressure relationship. Results: In NT rats, bolus infusion increased ICP and MAP, preserving CPP — confirming an intact intracranial baroreflex. In 2K1C rats, despite a similar elevation in ICP, MAP did not increase, resulting in a significant reduction in CPP and a higher P2/P1 ratio. During continuous infusion, both groups showed no change in MAP and sustained ICP elevation. However, 2K1C rats exhibited a marked decrease in CPP and a sharp increase in P2/P1, both absent in NT. The calculated ICC was significantly lower in 2K1C rats across both protocols. Conclusions: Renovascular hypertension impairs the intracranial baroreflex: the compensatory pressor response to increased ICP is blunted, leading to reduced CPP and further deterioration of intracranial compliance. These findings suggest that hypertensive patients may have reduced intracranial compensatory reserve, amplifying the pathological impact of transient volume fluctuations.

The objective was to quantify the effect of endovascular therapy (EVT) results of large-vessel occlusion (LVO) on brain tissue hydration, assessed by net water uptake (NWU). Materials and Methods. Ninety-three patients with EVT of acute ischemic stroke (AIS) due to acute LVO (men-44, women-49, median age 68.7) were included in this retrospective, non-randomized, single-center study. EVT was performed under general anesthesia with approved devices, including a stent retriever and aspiration catheters. Net water uptake (NWU) in ischemic zones was evaluated using non-contrasted computed tomography (CT). NWU was calculated using the well-known formula in the symmetrical zone of the brain, in admission and follow-up non-contrasted CT scans, 24 h after EVT. Results. Fifty-seven patients had successful arterial recanalization (Thrombolysis in Cerebral Infarction scale [TICI] 2b-3), while 36 patients had persistent or recurrent acute LVO (TICI 0-2a). The NWU median at admission was 3.4

A functional blood-brain barrier (BBB) is essential for CNS homeostasis, and its disruption is an early feature of both acute brain injury and chronic neurodegenerative disorders. Hypoxia induces BBB breakdown by triggering endothelial dysfunction, oxidative stress, metabolic dysregulation and thrombo-inflammatory signalling that compromise barrier integrity. However, strategies that restore BBB function remain limited. Here, we investigated whether photobiomodulation (PBM), a non-invasive light therapy, can rescue BBB dysfunction following acute hypoxic stress. Using a multicellular in vitro BBB model comprising immortalised human brain microvascular endothelial cells, pericytes and astrocytes, we induced hypoxic injury (6 h, 1% O2) and applied three PBM treatments during recovery. Hypoxia significantly reduced transendothelial electrical resistance (TEER), whereas PBM restored barrier function in endothelial monocultures and tri-cultures. Endothelial cells exhibited the most pronounced hypoxic response, characterised by increased expression of hypoxia-inducible factor-1α (HIF-1α), plasminogen activator inhibitor-1 and von Willebrand factor (vWF), all attenuated by PBM. Importantly, small interfering RNA-mediated knockdown of vWF partially recapitulated PBM-induced restoration of barrier integrity, identifying endothelial vWF as a mediator of recovery. PBM also reduced reactive oxygen species in hypoxic astrocytes and pericytes, indicating co-ordinated multicellular modulation. Together, these findings demonstrate that PBM restores BBB integrity following hypoxic insult by modulating endothelial thrombo-inflammatory signalling at the same time as reducing oxidative stress in glial cells. Rather than acting as a non-specific cytoprotective stimulus, PBM engages molecular pathways linked to endothelial activation. This work establishes a mechanistically informed platform for investigating BBB repair and highlights PBM as a strategy to protect vascular integrity in hypoxia-associated neurological disorders. KEY POINTS: Hypoxia is a major driver of blood-brain barrier (BBB) dysfunction, yet there are currently no targeted therapies that directly restore barrier integrity. Photobiomodulation (PBM) is a non-invasive low-level light intervention known to facilitate mitochondrial function and cellular stress responses. In a human in vitro BBB model, repeated PBM treatment restored transendothelial electrical resistance (TEER) 24 and 48 h after hypoxic injury, with endothelial rescue linked to downregulation of von Willebrand factor (vWF). PBM modulated oxidative stress, hypoxia signalling and thrombo-inflammatory pathways across endothelial cells, astrocytes and pericytes. These findings support PBM-driven modulation of endothelial signalling as a potential strategy to restore BBB integrity in hypoxia-associated neurological conditions.

Rationale and Objectives Repeated mild traumatic brain injury (mTBI), particularly from concussions, impairs cerebral perfusion and brain waste-clearance pathways, leading to lasting neurological deficits and elevated risk of neurodegeneration. Conventional pharmacological treatments targeting single pathways have shown limited efficacy in clinical trials. Photobiomodulation (PBM) has emerged as a promising noninvasive approach with the potential to improve both vascular function and clearance. Aim To determine whether transcranial PBM at 1267 nm, administered during the acute phase after repetitive concussion, improves cortical perfusion, oxygenation, intracranial compliance, meningeal lymphatic drainage, and neurological function in mice. Materials and Methods Male C57BL/6 mice (n=20) were randomized to PBM and sham groups and subjected to three repeated consecutive closed-head concussive impacts at 1.5-hour intervals to model repetitive mTBI. Transcranial PBM (1267 nm, 10 mW/cm², 5 mm diameter spot) was applied 4 h after the last impact for 45 min (three 10-minute sessions separated by 5-minute intervals). The 1267 nm wavelength lies within a biological transparency window that supports deeper transcranial penetration than shorter near-infrared wavelengths. Outcomes included cortical microcirculation, tissue oxygenation, intracranial compliance, meningeal lymphatic drainage, and neurological severity score. Statistical analyses were performed using two-way analysis of variance for multiple comparisons, with p < 0.05 considered significant. Results Repetitive concussion produced stepwise declines in cortical perfusion and oxygenation, reduced cerebral compliance, impaired lymphatic clearance, and worse neurological scores. PBM partially reversed these deficits compared with sham, improving microcirculation and oxygenation toward baseline levels, increasing cerebral compliance, restoring meningeal lymphatic drainage, and lowering neurological severity scores. Conclusion Acute transcranial PBM at 1267 nm mitigates cerebrovascular, biomechanical, and meningeal lymphatic dysfunction after repetitive concussion, with associated functional benefit. By concurrently improving perfusion, oxygen delivery, intracranial compliance, and lymphatic drainage, PBM represents a mechanistically grounded, noninvasive candidate therapy for early adjunct intervention after mTBI.

The aim of the study was to evaluate changes in eye movement conjugation in healthy volunteers in response to transcranial photobiomodulation (tPBM). Materials and Methods. 54 healthy volunteers (23 men, 31 women; median age was 23.5 years) were included in this retrospective, non-randomized study. Eye tracking (ET) was performed using the iPad app EyeTracker with a sampling rate of 20 Hz before and after 10 min tPBM (810 nm). The tracker calculated angular velocities in the vertical and horizontal planes (AV; vertical and horizontal). Data are shown as a median [interquartile range]. Pearson’s correlation coefficients were used to assess agreement between computed variables. This coefficient value was designated as the vergence reactivity index (VRx), which reflects the eye movement conjugation. The differences were determined using the Wilcoxon T-criterion. The level of significance was p < 0.05. Results. Vertical and horizontal VRx after tPBM were significantly higher than before the procedure: 0.878 [0.843; 0.902] vs. 0.783 [0.702; 0.829], p < 0.001, respectively and 0.875 [0.834; 0.912] vs. 0.927 [0.921; 0.93], p < 0.001, respectively. Conclusion. Transcranial PBM causes a significant increase in vertical and horizontal vergence indices, which indicates an improvement in eye movement conjugation in healthy volunteers.

PURPOSE:The aim was to study visual perception changes based on eye-tracking data assessments in response to transcranial photobiomodulation (t-PBM) in young, healthy subjects. MATERIAL AND METHODS:Our non-randomized single-center study involving 53 young, healthy volunteers (22 men and 31 women). The eye tracking procedure (EyeTracker, BVG Software Group LLC, CA, USA) was carried out before and immediately after t-PBM (Elmedlife H, RF). Data were expressed as a median [interquartile range]. Statistical analysis was performed using the T- criterion Wilcoxon. The significance level was preset p < 0.05. RESULTS:Vertical vergence reactivity indexes (VRx) after t-PBM were significantly higher than before 0.881 [0.841; 0.914] vs. 0.784 [0.711; 0.832], p < 0.05, respectively. Horizontal VRx before t-PBM were significantly lower than after t-PBM 0.893 [0.822; 0.935] vs. 0.920 [0.917; 0.929], p < 0.05. CONCLUSION:Transcranial PBM improves visual perception in young, healthy volunteers, as reflected by a significant increase in both vergence reactivity indices.

Intracranial pressure (ICP) is pressure within the cranium, between 5 and 15 mmHg in a normal brain, and is influenced by the dynamic balance between brain tissue, cerebrospinal fluid (CSF) and cerebral blood volume. ICP is vital for cerebral health, impacting outcomes in various neurological conditions. Disruptions, such as cerebral haemorrhage, hydrocephalus and malignant hypertension, can lead to elevated ICP, a dangerous condition known as intracranial hypertension (IH). Systemic hypertension significantly impacts cerebral health by causing microvascular damage, dysfunction of the blood-brain barrier (BBB) and impairment of intracranial compliance (ICC). This increases the risk of IH), cerebral ischaemia, neuroinflammation and lacunar infarction, further worsening neurological dysfunction. This review describes the complex relationship between hypertension and ICP regulation, focusing on the mechanisms underlying ICP and ICC adjustments in hypertensive conditions and emphasizing the role of BBB integrity and cerebral blood flow (CBF) dynamics. It discusses how the sympathetic output might change the regulation of CBF and the maintenance of ICP, highlighting how hypertensive conditions can impair this mechanism, increasing the risk of cerebral ischaemia. The neurovascular unit, including astrocytes and microglia, plays a significant role in this process, contributing to IH in hypertensive patients. Understanding the effects of hypertension on ICP and ICC could lead to therapies aimed at preserving BBB integrity, reducing inflammation and improving cerebral compliance, potentially preventing brain dysfunction and reducing stroke risk in hypertensive patients. This review underscores the need for early detection and intervention to mitigate the severe consequences of uncontrolled hypertension on cerebral health.