Long-term development of dynamic changes in neurovascular coupling after acute temporal lobe epilepsy

Abstract

Epilepsy is an abnormal brain state that may be induced by synchronous neuronal activation and also abnormalities in energy metabolism or the oxygen supply vascular system. Neurovascular coupling (NVC), the relationship between neuron, capillary, and penetrating artery, remains unexplored on a fine-scale with respect to the pathology process after acute temporal lobe epilepsy (TLE). Here we use two-photon microscopy (TPM) to provide high temporal-spatial resolution imaging to identify changes in NVC during spontaneous and electro-stimulated (ES) states in awake mice. Implantation of a long-term craniotomy window allowed TPM recording of the pathological development after the acute Kainic Acid temporal lobe epilepsy model. Our results provide direct evidence that the capillary and penetrating artery are not correlated to rhythmic neuronal activity during acute epilepsy. During the CSD period, NVC shows a strong correlation. We demonstrate that NVC exhibits nonlinear dynamics after status epilepticus. Furthermore, the vascular correlation to neuronal signals in spontaneous and ES states shows dynamic changes which correlate to the evolution after acute TLE. Understanding NVC in all TLE stages, from the acute through the TLE pathological development, may provide new therapeutic pathways.

Keywords: Cortical spreading depression; Epilepsy; Neurovascular coupling; Temporal lobe epilepsy; Two photon imaging.