Hyperglycemia aggravates ischemic brain damage via ERK1/2 activated cell autophagy and mitochondrial fission

• DOI: 10.3389/fendo.2022.928591
• Publication Date: 2022-08-05T06:33:03Z
• Authors: Ping Liu; Xiao Yang; Jianguo Niu; Changchun Hei
• Keywords: 0301 basic medicine; cell autophagy; MAP Kinase Signaling System; Mitochondrial Dynamics; Diseases of the endocrine glands. Clinical endocrinology; Streptozocin; Brain Ischemia; Mitochondrial Proteins; Rats, Sprague-Dawley; 03 medical and health sciences; Endocrinology; Autophagy; Animals; Drp-1; ERK1/2; mitochondrial fission; Brain; RC648-665; Rats; 3. Good health; Stroke; Hyperglycemia; Reperfusion Injury; cerebral ischemic injury; Beclin-1; hyperglycemia

Hyperglycemia is one of the major risk factors for stroke and recurrence, leading to aggravated neuronal damage after cerebral ischemia/reperfusion (I/R). ERK1/2 signaling pathway plays a vital role in ischemic injury. However, hyperglycemia-aggravated brain not clear. Streptozotocin (STZ; 50 mg/kg)-induced diabetes (blood glucose ≥12 mmol/L) or control groups adult Sprague-Dawley rats were further subdivided into I/R (carotid artery/vein clamping), + PD98059 (I/R plus inhibitor), Sham-operated (n = 10 each). Neurobehavioral status (Neurological behavior scores) volume infarction (TTC staining); mitochondrial potential (JCI ratio test) cell apoptosis (TUNEL assay); RAS protein expression, phosphorylated/total Drp-1 (Dynamic-related 1) levels (Western blotting); fusion-related proteins mitofusin-1/2 (Mfn1/2), optic atrophy (OPA-1) fission 1 (Fis1), autophagy-associated Beclin-1, LC3-I/II P62 blotting immunohistochemistry) analyzed. The group demonstrated better neurobehavior on 1st (p < 0.05) 3rd day 0.01) than group. Compared Sham group, brought about <0.01). treatment with showed an improved situation faster recovery less cells 0.01). had higher-level expression phosphorylated mellitus (DM) treated decreased p-ERK1/2, p-Drp-1, Fis1, P62, but increased Mfn1/2 OPA-1 worsens ischemia/reperfusion-induced via activated autophagy fission.