The clinical significance of vertebral artery (VA) hypoplasia is under discussion. The aim of this retrospective study is to evaluate a hypothesis of a possible causal link between VA hypoplasia (VAH) and the incidence of posterior circulation stroke (PCS) or TIA depending on the degree of VAH and vascular risk factors. A total of 367 symptomatic (PCS or TIA) and 742 asymptomatic subjects, were selected to participate in the study. The extracranial arteries were examined by ultrasound. VAH was defined as VA diameter in entire course <3 mm, although different degrees of VAH were examined. All the symptomatic patients underwent MRI or CT and MRA or CTA. The study assessed all the subjects in terms of their age, gender, co-risk factors (hypertension, hyperlipidemia, diabetes mellitus, peripheral arterial diseases, atrial fibrillation, myocardial infarction), as well as height of 180 healthy volunteers. VAH, regardless of the degree of severity, was more frequent in patients with non-cardioembolic PCS or TIA rather than in asymptomatic patients. The increasing degree of hypoplasia in patients under 65 years of age was a predictor of PCS/TIA, OR = 1.8, 95 % CI: 1.3-2.5; p < 0.001. In subjects older than 65 years of age, this association failed. Only in patients aged under 50, VAH was significantly more frequent in the TIA group rather than in the PCS group (68.2 % and 50 %, respectively; p = 0.047). The optimal VA diameter cutoff point separating PCS/TIA and asymptomatic group was 2.7 mm. This value may vary in different populations, because VA diameter showed a significant dependence on sex as well as anthropometric parameters (height). With the increasing degree of VAH, the likelihood of the occurrence of the distal VA part stenosis/occlusion was growing (OR = 1.6, 95 % CI: 1.2-2.1; p = 0.002). The distal VA stenosis/occlusion was likely to occur where the VA diameter was <2.2 mm. The impact of the VAH on PCS/TIA and its pathogenetic mechanism was significantly influenced by age. The cutoff point of VA diameter, affecting the occurrence of PCS in different populations may vary because VA diameter depends on gender and anthropometric parameters (especially height).

Background and Objectives: The aim of this study was to explore the association between the cerebral autoregulation (CA) index, the pressure reactivity index (PRx), the patient’s clinical outcome, and the quality of arterial blood pressure (ABP(t)) and intracranial blood pressure (ICP(t)) signals by comparing two filtering methods to derive the PRx. Materials and Methods: Data from 60 traumatic brain injury (TBI) patients were collected. Moving averaging and FIR (Finite Impulse Response) filtering were performed on the ABP(t) and ICP(t) signals, and the PRx was estimated from both filtered datasets. Sensitivity, specificity, and receiver-operating characteristic (ROC) curves with the area under the curves (AUCs) were determined using patient outcomes as a reference. The outcome chosen for comparison among the two filtering methods were mortality and survival. Results: The FIR filtering approach, compared with clinical outcome, had a sensitivity of 70%, a specificity of 81%, and a level of significance p = 0.001 with an area under the curve (AUC) of 0.78. The moving average filtering method compared with the clinical outcome had a sensitivity of 58%, a specificity of 72%, and a level of significance p = 0.054, with an area under the curve (AUC) of 0.66. Conclusions: The FIR (optimal) filtering approach was found to be more sensitive for discriminating between two clinical outcomes, namely intact (survival) and impaired (death) cerebral autoregulation for TBI treatment decision making.

Background and Objectives: An altered sympathetic function is established in primary arterial hypertension (PAH) development. Therefore, PAH could be targeted by applying an electric current to the medulla where reflex centers for blood pressure control reside. This study aims to evaluate the electric caudal ventrolateral medulla (CVLM) stimulation effect on blood pressure and animal survivability in a freely moving rat model. Materials and Methods: A total of 20 Wistar rats aged 12–16 weeks were randomly assigned to either: the experimental group (n = 10; electrode tip implanted in CVLM region) or the control group (n = 10; tip implanted 4 mm above the CVLM in the cerebellum). After a period of recovery (4 days), an experimental phase ensued, divided into an “OFF stimulation” period (5–7 days post-surgery) and an “ON stimulation” period (8–14 days post-surgery). Results: Three animals (15%, one in the control, two in the experimental group) dropped out due to postoperative complications. Arterial pressure in the experimental group rats during the “OFF stimulation” period decreased by 8.23 mm Hg (p = 0.001) and heart rate by 26.93 beats/min (p = 0.008). Conclusions: From a physiological perspective, CVLM could be an effective deep brain stimulation (DBS) target for drug-resistant hypertension: able to influence the baroreflex arc directly, having no known direct integrative or neuroendocrine function. Targeting the baroreflex regulatory center, but not its sensory or effector parts, could lead to a more predictable effect and stability of the control system. Although targeting neural centers in the medullary region is considered dangerous and prone to complications, it could open a new vista for deep brain stimulation therapy. A possible change in electrode design would be required to apply CVLM DBS in clinical trials in the future.

Glial cells are fundamental for the pathophysiology of all neurological disorders. Astrocytes, the primary home-ostatic cells of the central nervous system (CNS), exhibit species-specific characteristics, with human astrocytes specifically displaying unique structural and functional features. It is thus essential to investigate human-specific astrocytic responses to neuropathology using human-relevant models. Varicose projection (VP) astrocytes, traditionally considered specific to humans and apes, were suggested to reflect pathological burden, albeit direct evidence linking them to neurological diseases has been lacking. Here, we demonstrate for the first time that VP astrocytes are present in mice and tigers ( Panthera tigris ) and we provide evidence from four distinct human-based models that VP astrocytes are not a distinct physiological astrocyte subtype but rather a novel class of reactive astrocytes associated with neuropathology. Using human induced pluripotent stem cell (hiPSC)-derived astrocytes, mixed neural cultures, and cortical organoids, we showed that VP astrocytes are induced by pro-inflammatory cytokines interleukin-1 β (IL-1 β ) and tumor necrosis factor- α (TNF- α ) or LPS. Notably, cytokine withdrawal reverses the VP phenotype of astrocytes, indicating that it is a transient, inflammation-dependent state. We characterized the distinctive components of varicosities, including markers for extracellular vesicles, mitochondria, Golgi and endoplasmic reticulum components, suggesting roles in cellular stress responses and metabolic dysregulation. We further validated the pathological relevance of VP astrocytes by documenting their significant enrichment in postmortem brain samples from patients with several neurodegenerative diseases including as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, as well as in surgical resections from patients with epilepsy due to hippocampal sclerosis or brain tumors, including previously unreported subcortical regions such as basal ganglia. Additionally, we identified a higher number of VP astrocytes also in mouse astrocytes upon treatment with pro-inflammatory cytokines, suggesting that formation of VP astrocytes is an evolutionarily conserved astrocytic response to neuroinflammation. Our findings point to VP astrocytes as a novel reactive astrocyte subtype closely linked to neuropathology, highlighting their potential as biomarkers and therapeutic targets in neurological diseases. This study lays the groundwork for future investigations into the mechanisms driving VP astrocyte formation and their broader implications in neuropathology.

The control circuits of blood pressure have a strong neural regulatory element important in the pathogenesis of essential drug-resistant hypertension. Targeting lower medullary neural control mechanisms of blood pressure by electrical stimulation could be beneficial, and therefore, a novel device is needed. This paper presents a remotely programmable deep brain stimulator with an invasive continuous blood pressure monitoring system in a non-tethered rat model. The device is designed for lower medullary deep brain stimulation research with minimal interference to a daily animal routine. Electrodes were implanted in the caudal ventrolateral medulla. Animal survivability, catheter patency rates, and device data drift were evaluated. Eight out of ten rats survived the surgery and testing period with no or mild temporary neurological compromise. The study revealed that carotid catheters filled with heparinized glycerol ensure better catheter patency rates and blood pressure transduction. There was no significant drift in the device’s pressure sensitivity during the experiment. To our knowledge, this is the first experimental study to show considerable animal survival after lower medullary implantation. Combining the ability to measure and monitor invasive blood pressure with a closed-loop brain pulse generator in a single device could be of potential value in future hemodynamic animal research.