Involvement of phosphatidylinositol 3-kinase/protein kinase B signaling pathway in early brain injury after subarachnoid hemorrhage and its mechanism

Abstract

Objective To explore the role of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in early brain injury after subarachnoid hemorrhage (SAH) and its possible mechanism in rats. Methods Ninety healthy male SD rats were randomly divided into 5 groups (n=18) according to the random number table, namely sham-operated group, SAH group, vehicle control group, SAH+PI3K/Akt pathway agonist group (group A), and SAH+PI3K/Akt pathway inhibitor group (group I, n=18). Rat SAH models of the later 4 groups were established by intravascular puncture; rats in the vehicle control group, group A, and group I were given 10 μL dimethyl sulfoxide (DMSO), insulin-like growth factor (IGF-1, 1 μg/10 μL), and Ly294002 (25 μg/10 μL) solution, respectively, before model making. After 24 h of intravascular puncture, modified Garcia nerve function scale was used to evaluate the motor function, dry-wet weight method was used to detect the water content of the brain tissues, and immunofluorescence staining was employed to observe the β-amyloid precursor protein (β-APP)/β tubulin III positive expressions in the subcortical white matter, and Western blotting was employed to detect the β-APP, and total (t)- and phosphorylated (p)-PI3K and Akt protein expressions in the brain tissues; one month after modeling, HE staining was used to observe the changes of cell structure after cerebral edema. Results As compared with the sham-operated group, SAH model group had significantly lower modified Garcia nerve function scale scores, significantly increased brain water content, significantly larger number of β-APP/β tubulin III positive cells, statistically increased β-APP protein expression, and significantly increased t-PI3K, and t-Akt protein expressions (P<0.05). As compared with the SAH model group, group A had significantly higher modified Garcia nerve function scale scores, significantly decreased brain water content, significantly smaller number of β-APP/β tubulin III positive cells, statistically decreased β-APP protein expression, and significantly increased p-PI3K and p-Akt protein expressions (P<0.05). As compared with group A, group I had significantly lower modified Garcia nerve function scale scores, significantly increased brain water content, significantly larger number of β-APP/β tubulin III positive cells, statistically increased β-APP protein expression, and significantly decreased p-PI3K and p-Akt protein expressions (P<0.05). HE staining showed serious morphological damage. Conclusion PI3K/Akt signaling pathway plays an important role in early brain injury after SAH in rats; early stimulation of PI3K/Akt signaling pathway activation can alleviate early brain injury after SAH, and the mechanism may be related to regulation of axonal injury in white matter after SAH. Key words: Subarachnoid hemorrhage; Early brain injury; Phosphatidylinositol 3-kinase/protein kinase B signal pathway; Axonal injury