Microvascular changes associated with epilepsy: A narrative review

Abstract

The blood-brain barrier (BBB) is dysfunctional in temporal lobe epilepsy (TLE). In this regard, microvascular changes are likely present. The aim of this review is to provide an overview of the current knowledge on microvascular changes in epilepsy, and includes clinical and preclinical evidence of seizure induced angiogenesis, barriergenesis and microcirculatory alterations. Anatomical studies show increased microvascular density in the hippocampus, amygdala, and neocortex accompanied by BBB leakage in various rodent epilepsy models. In human TLE, a decrease in afferent vessels, morphologically abnormal vessels, and an increase in endothelial basement membranes have been observed. Both clinical and experimental evidence suggests that basement membrane changes, such as string vessels and protrusions, indicate and visualize a misbalance between endothelial cell proliferation and barriergenesis. Vascular endothelial growth factor (VEGF) appears to play a crucial role. Following an altered vascular anatomy, its physiological functioning is affected as expressed by neurovascular decoupling that subsequently leads to hypoperfusion, disrupted parenchymal homeostasis and potentially to seizures”. Thus, epilepsy might be a condition characterized by disturbed cerebral microvasculature in which VEGF plays a pivotal role. Additional physiological data from patients is however required to validate findings from models and histological studies on patient biopsies.

Vascular topology and blood flow are acutely impacted by experimental febrile status epilepticus

“…Altered vascular topology has been reported both acutely and long-term in adult models of status epilepticus. 22 To our knowledge there are no hyperacute (hours post SE) studies examining the vascular morphology nor studies examining the vascular consequences of FSE. Thus, Ndode-Ekane in a pilocarpine model of status epilepticus (SE) found reduced hippocampal vessel density, vessel length accompanied by increased blood-brain barrier (BBB) leak at 2 days post SE using immunohistochemical staining.…”

“…Increased vascular densities were found in the cortex and amygdala, days and weeks after adult rat pilocarpine and kainate-induced SE. 29,45 Within the hippocampus the overwhelming evidence is for increased microvascular density days to weeks after induced adult SE (see Table 1 in Marcon 22 for a concise summary). In our study we found increased vessel length in the hippocampus of FSE pups at 2 hrs after the cessation of SE that was mirrored by our fractal analyses (Figure 5(c)).…”

Variants in BRWD3 associated with X‐linked partial epilepsy without intellectual disability

“…In the present study, the missense variants associated with epilepsy were located in WD40 repeat domain or bromodomain. These evidences suggest that WD40 repeat domains and bromodomains of BRWD3 may play a crucial role in the pathophysiology of epileptogenesis by affecting cell signal transduction, epigenetic signaling reading, level of neurotransmitters, and neurovascular changes 33,34 . Further studies on the pathological consequences/neurological dysfunction are required to elucidate the essential link between the BRWD3 variants and epilepsy.…”

Epileptic seizure induced by rapid repetitive limb movements

“…Thus, evaluating the relationship between cerebral microvasculature and epilepsy may lead to the development of new therapeutic targets. 8 …”