Neuroelectric Mechanisms of Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage

Abstract

Delayed cerebral ischemia (DCI) remains a challenging but very important condition, because DCI is preventable and treatable for improving functional outcomes after aneurysmal subarachnoid hemorrhage (SAH). The pathologies underlying DCI are multifactorial. Classical approaches to DCI focus exclusively on preventing and treating the reduction of blood flow supply. However, recently, glutamate-mediated neuroelectric disruptions, such as excitotoxicity, cortical spreading depolarization and seizures, and epileptiform discharges, have been reported to occur in high frequencies in association with DCI development after SAH. Each of the neuroelectric disruptions can trigger the other, which augments metabolic demand. If increased metabolic demand exceeds the impaired blood supply, the mismatch leads to relative ischemia, resulting in DCI. The neuroelectric disruption also induces inverted vasoconstrictive neurovascular coupling in compromised brain tissues after SAH, causing DCI. Although glutamates and the receptors may play central roles in the development of excitotoxicity, cortical spreading ischemia and epileptic activity-related events, more studies are needed to clarify the pathophysiology and to develop novel therapeutic strategies for preventing or treating neuroelectric disruption-related DCI after SAH. This article reviews the recent advancement in research on neuroelectric disruption after SAH.

Effects of New-Generation Antiepileptic Drug Prophylaxis on Delayed Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage

“…DCI occurs via a complex interplay among several concurrent processes including cerebral (angiographic) vasospasm, cerebral microcirculatory and neuroelectric disturbances including CSDs [6,9]. It was reported that the development of late-onset epileptiform discharges might cause DCI by triggering CSDs, or to a lesser extent directly [23].…”

“…It was reported that the development of late-onset epileptiform discharges might cause DCI by triggering CSDs, or to a lesser extent directly [23]. CSD clusters are considered to induce inverted vasoconstrictive neurovascular coupling and then cerebral microcirculatory disturbances in compromised brain tissues after severe SAH, causing DCI [9,10]. Although seizure and CSD are biologically distinct phenomena, they are interlinked, and can trigger each other, worsening metabolic supply-demand mismatch and leading to progression of DCI after SAH [9].…”

“…Recently, neuroelectric disruptions such as cortical spreading depolarization (CSD) and epileptiform activity have been revealed to be an important contributor to the development of DCI after SAH [9]. CSDs and epileptiform activities may have similar toxic effects such as an increase in metabolic demand, arteriolar constriction via inverse neurovascular coupling, microthrombosis formation with platelet activation, and neuroin ammatory reactions, all of which may cause DCI [9,10].…”

“…Recently, neuroelectric disruptions such as cortical spreading depolarization (CSD) and epileptiform activity have been revealed to be an important contributor to the development of DCI after SAH [9]. CSDs and epileptiform activities may have similar toxic effects such as an increase in metabolic demand, arteriolar constriction via inverse neurovascular coupling, microthrombosis formation with platelet activation, and neuroin ammatory reactions, all of which may cause DCI [9,10]. Because CSDs and epileptiform activities trigger each other to augment their actions and to worsen the metabolic supplydemand mismatch [9], some antiepileptic drugs may antagonize CSDs as well as epileptiform discharges, and resultantly prevent DCI [11].…”

“…CSDs and epileptiform activities may have similar toxic effects such as an increase in metabolic demand, arteriolar constriction via inverse neurovascular coupling, microthrombosis formation with platelet activation, and neuroin ammatory reactions, all of which may cause DCI [9,10]. Because CSDs and epileptiform activities trigger each other to augment their actions and to worsen the metabolic supplydemand mismatch [9], some antiepileptic drugs may antagonize CSDs as well as epileptiform discharges, and resultantly prevent DCI [11]. In fact, recent experimental studies reported that some antiepileptic drugs had neuroprotective effects against post-SAH pathologies [12,13].…”