Cerebrovascular glycocalyx damage and microcirculation impairment in patients with temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is increasingly associated with blood-brain barrier dysfunction and microvascular alterations, yet the pathophysiological link is missing. An important barrier function is exerted by the glycocalyx, a gel-like layer coating the endothelium. To explore such associations, we used intraoperative videomicroscopy to quantify glycocalyx and microcirculation properties of the neocortex and hippocampus of 15 patients undergoing resective brain surgery as treatment for drug-resistant TLE, and 15 non-epileptic controls. Fluorescent lectin staining of neocortex and hippocampal tissue was used for blood vessel surface area quantification. Neocortical perfused boundary region, the thickness of the glycocalyx' impaired layer, was higher in patients (2.64 ± 0.52 µm) compared to controls (1.31 ± 0.29 µm), P < 0.01, indicative of reduced glycocalyx integrity in patients. Moreover, erythrocyte flow velocity analysis revealed an impaired ability of TLE patients to (de-)recruit capillaries in response to changing metabolic demands (R2 = 0.75, P < 0.01), indicating failure of neurovascular coupling mechanisms. Blood vessel quantification comparison between intraoperative measurements and resected tissue showed strong correlation (R2 = 0.94, P < 0.01). This is the first report on in vivo assessment of glycocalyx and microcirculation properties in TLE patients, confirming the pivotal role of cerebrovascular changes. Further assessment of the cerebral microcirculation in relation to epileptogenesis might open avenues for new therapeutic targets for drug-resistant epilepsy.

Microvascular changes associated with epilepsy: A narrative review.

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.