Subarachnoid hemorrhage mediates human neocortical network, membrane potential, and action potential bursting via glutamate receptors.

Subarachnoid hemorrhage (SAH) is a life-threatening neurological emergency with high mortality and morbidity rates. Despite its severity, the acute and direct neuronal effects of SAH remain poorly understood, particularly in human brain tissue. To address this gap, we applied cerebrospinal fluid from individuals with SAH (SAH-CSF) to human neocortical slices and examined neuronal activity and intrinsic properties. We found that SAH-CSF significantly increased population-wide neuronal activity, depolarized membrane potential, and either elevated firing rates or induced depolarization block of action potentials in these human neocortical slices. Notably, these neuronal changes were reversible upon washout of the SAH-CSF. Furthermore, kynurenic acid (KYNA), a glutamate receptor antagonist, effectively prevented SAH-CSF-induced neuronal changes. Together, these findings revealed key neuronal consequences of SAH-CSF in human brain tissue and suggest that glutamate receptor antagonists may offer therapeutic potential for SAH.