Blood−brain barrier breakdown and neovascularization processes after stroke and traumatic brain injury

Abstract

Purpose of review Angiogenesis or vascular reorganization plays a role in recovery after stroke and traumatic brain injury (TBI). In this review, we have focused on two major events that occur during stroke and TBI from a vascular perspective – what is the process and time course of blood–brain barrier (BBB) breakdown? and how does the surrounding vasculature recover and facilitate repair? Recent findings Despite differences in the primary injury, the BBB changes overlap between stroke and TBI. Disruption of BBB involves a series of events: formation of caveolae, trans and paracellular disruption, tight junction breakdown and vascular disruption. Confounding factors that need careful assessment and standardization are the severity, duration and extent of the stroke and TBI that influences BBB disruption. Vascular repair proceeds through long-term neovascularization processes: angiogenesis, arteriogenesis and vasculogenesis. Enhancing each of these processes may impart beneficial effects in endogenous recovery. Summary Our understanding of BBB breakdown acutely after the cerebrovascular injury has come a long way; however, we lack a clear understanding of the course of BBB disruption and BBB recovery and the evolution of individual cellular events associated with BBB change. Neovascularization responses have been widely studied in stroke for their role in functional recovery but the role of vascular reorganization after TBI in recovery is much less defined.

Sevoflurane protects rat brain endothelial barrier structure and function after hypoxia-reoxygenation injury

“…Blood-brain barrier disruption is highly relevant in the pathogenesis of secondary brain damage after brain injury [12, 25]. In the present study, we show for the first time that sevoflurane treatment during the early reoxygenation period following severe hypoxia promotes the maintenance of BBB structure and function in rat brain endothelial cells.…”

Autoantibodies in Neuropsychiatric Disorders

“…The same study also relates the effects of the autoantibodies to the patients' history of birth complications or neurotrauma indicating possible BBB insufficiency. This hypothesis is further supported by the findings that increased prevalence of psychiatric comorbidity in diseases is associated with BBB dysfunction, including systemic lupus erythematous (SLE) [46][47][48], stroke [49][50][51][52], epilepsy [53,54] and autoimmune encephalitis [45,55]. An increased albumin ratio in CSF to serum in patients with MDD and schizophrenia further suggests increased BBB permeability [56].…”

Astrocytic tight junctions control inflammatory CNS lesion pathogenesis

“…Primary human fetal astrocyte cultures were established from 3 different brains as previously described (8)(9)(10)(11)(12) weeks old, at least 5 per condition per time point, on the C57BL/6 background) were anesthetized using isoflurane and placed into a stereotactic frame (Kopf). AdIL-1 or AdDL70 control (AdCtrl) (10 7 PFU) was microinjected into the cerebral cortex at y = 1 mm caudal to bregma, x = 2 mm, z = 1.5 mm as previously described (18).…”

“…Previous reports identified breakdown of the endothelial BBB as a critical event in lesion pathogenesis in conditions including MS, NMO, and viral meningoencephalitis (10)(11)(12). Establishment and maintenance of the endothelial barrier depend on astrocytes (13) and pericytes (14,15), and both are also linked to BBB disruption in disease (14,16).…”