Dexmedetomidine Inhibits Endoplasmic Reticulum Stress Response and Improves Neurological Function After Traumatic Brain Injury in Rats

Abstract

Dexmedetomidine (DEX) can inhibit neuronal apoptosis. There are multiple secondary lesions following traumatic brain injury (TBI). Our study evaluated the application of DEX in TBI by observing neurological impairment score, brain edema, nerve cells apoptosis, and endoplasmic reticulum stress response (ERS). SD rats were selected to establish TBI model using modified Feeney method and then randomly divided into sham operation group (A), TBI group (B), TBI + DEX group (C), and TBI + DEX + endoplasmic reticulum stress inducer 2-deoxyglucose (2-DG) group (D). The neurological injury severity score (mNSS) was measured on day 1, 3, and 7 after injury. The water content of brain tissue was measured. The pathology of brain tissue was observed on the 7th day after craniocerebral injury. Caspase-12 and IRE-1 were determined by Western blot. Apoptosis was assessed by TUNEL assay. CHOP and Glucose Regulatory Protein 78 (GRP78) expressions were detected by immunohistochemistry (IHC). Compared with group A, mNSS scores, brain water content, and neuronal apoptosis were increased, and caspase-12, IRE-1, CHOP, and GRP78 proteins were upregulated in groups B, C, and D (P < 0.05). Compared to group B, the neurological function was improved, brain water content and neuronal apoptosis were decreased, and caspase-12, IRE-1, CHOP, and GRP78 protein expressions were reduced in group C (P < 0.05). Neurological impairment was aggravated, brain water content and nerve cell apoptosis were increased, and caspase-12, IRE-1, CHOP, and GRP78 protein expressions were upregulated in group D compared to group C (P < 0.05). DEX treatment can alleviate brain edema after TBI and inhibit neuronal apoptosis, which has neuroprotective effects. Its mechanism may be related to ERS after TBI inhibition.