TAT-PEP alleviated cognitive impairment by alleviating neuronal mitochondria damage and apoptosis after cerebral ischemic reperfusion injury

Abstract

AbstractPaired immunoglobulin-like receptor B (PirB) has been identified as a receptor for myelin-associated inhibitory proteins (MAIs), which plays a vital role in axonal regeneration, synaptic plasticity, and neuronal survival after stroke. In our previous study, a transactivator of transcription-PirB extracellular peptide (TAT-PEP) was generated, which can block the interactions between MAIs and PirB. We found that TAT-PEP treatment enhanced axonal regeneration, CST projection, and improved long-term neurobehavioral functional recovery after stroke through its effects on PirB-mediated downstream signaling molecules. However, the impact of TAT-PEP on cognitive function recovery and neuronal survival also needs to explore. Here, we investigated thatpirbRNAi alleviated neuronal injury by inhibiting PirB expression after exposure to oxygen-glucose deprivation (OGD) in vitro. Moreover, TAT-PEP treatment attenuated brain infarct volume and promoted neurobehavioral function and cognitive function recovery. This study further found TAT-PEP exerted neuroprotection by alleviating neuronal degeneration and apoptosis after ischemic reperfusion injury. The study also showed that TAT-PEP enhanced neuronal survival and reduced the release of lactate dehydrogenase (LDH)in vitro. Furthermore, the results indicated TAT-PEP decreased malondialdehyde (MDA) levels, increased superoxide dismutase (SOD) activity, and alleviated reactive oxygen species (ROS) accumulation of neurons exposed to OGD injury. The possible mechanism was TAT-PEP could help neuronal mitochondria damage and affect the expression of cleaved Caspase3, Bax, and Bcl-2. Our findings suggest that PirB overexpression in neurons after suffering ischemic reperfusion injury-induced neuronal mitochondria damage, oxidative stress, and apoptosis. This study also indicated that TAT-PEP might represent a highly productive neuroprotective agent displaying therapeutic potential for stroke by alleviating neuronal oxidative stress, mitochondria damage, degeneration, and apoptosis against ischemic stroke.