Frequency selective neuronal modulation triggers spreading depolarizations in the rat endothelin-1 model of stroke.
Paolo BazzigaluppiJames MesterIllsung L JooIliya WeisspapirAdrienne DorrMargaret M KoletarTina L BeckettHouman KhosravaniPeter CarlenBojana StefanovicPublished in: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (2021)
Ischemia is one of the most common causes of acquired brain injury. Central to its noxious sequelae are spreading depolarizations (SDs), waves of persistent depolarizations which start at the location of the flow obstruction and expand outwards leading to excitotoxic damage. The majority of acute stage of stroke studies to date have focused on the phenomenology of SDs and their association with brain damage. In the current work, we investigated the role of peri-injection zone pyramidal neurons in triggering SDs by optogenetic stimulation in an endothelin-1 rat model of focal ischemia. Our concurrent two photon fluorescence microscopy data and local field potential recordings indicated that a ≥ 60% drop in cortical arteriolar red blood cell velocity was associated with SDs at the ET-1 injection site. SDs were also observed in the peri-injection zone, which subsequently exhibited elevated neuronal activity in the low-frequency bands. Critically, SDs were triggered by low- but not high-frequency optogenetic stimulation of peri-injection zone pyramidal neurons. Our findings depict a complex etiology of SDs post focal ischemia and reveal that effects of neuronal modulation exhibit spectral and spatial selectivity.
Keyphrases
- cerebral ischemia
- brain injury
- high frequency
- subarachnoid hemorrhage
- red blood cell
- ultrasound guided
- oxidative stress
- optical coherence tomography
- atrial fibrillation
- single molecule
- spinal cord
- high resolution
- magnetic resonance
- radiation therapy
- risk assessment
- multiple sclerosis
- genome wide
- gene expression
- squamous cell carcinoma
- electronic health record
- data analysis
- artificial intelligence
- mass spectrometry
- human health
- case control
- white matter
- mechanical ventilation
- extracorporeal membrane oxygenation
- atomic force microscopy