The neuroprotection of controlled decompression after traumatic epidural intracranial hypertension through suppression of autophagy via PI3K/Akt signaling pathway

Yuanyuan Che; Wei Wu; Xiao Qian; Zhengwei Sheng; Wang Zhang; Jie Zheng; Junhui Chen; Yuhai Wang

doi:10.1016/j.heliyon.2023.e23753

The neuroprotection of controlled decompression after traumatic epidural intracranial hypertension through suppression of autophagy via PI3K/Akt signaling pathway

Heliyon. 2023 Dec 19;10(1):e23753. doi: 10.1016/j.heliyon.2023.e23753. eCollection 2024 Jan 15.

Authors

Yuanyuan Che^{1

2}, Wei Wu³, Xiao Qian^{1

2}, Zhengwei Sheng^{1

2}, Wang Zhang^{1

2}, Jie Zheng^{1

2}, Junhui Chen^{1

2}, Yuhai Wang^{1

2}

Affiliations

¹ Wuxi Clinical College of Anhui Medical University, The Fifth Clinical Medical College of Anhui Medical University, Wuxi, Jiangsu, 214044, China.
² Department of Neurosurgery, The 904th Hospital of PLA, Wuxi, Jiangsu, China.
³ Department of Laboratory, The 904th Hospital of PLA, Wuxi, Jiangsu, China.

Abstract

Acute intracranial hypertension (AIH) is a common and tricky symptom that inflicts upon patients after traumatic brain injury (TBI). A variety of clinical options have been applied for the management of AIH, such as physiotherapy, medication, surgery and combination therapy. Specifically, controlled decompression (CDC) alleviates the extent of brain injury and reduces the incidence of a series of post-TBI complications, thereby enhancing the prognosis of patients suffering from acute intracranial hypertension. The objective of the present project is to illuminate the potential molecular mechanism that underlies the neuroprotective effects of CDC in a rat model of traumatic epidural intracranial hypertension (TEIH). Herein, we observed the functional recovery, the degree of brain edema, the level of apoptosis, the expressions of neuronal cell autophagy-related signaling pathway proteins (including Akt, p-Akt, LC3 and Beclin-1) in rat TEIH model at 24 h post-surgery. The results showed in comparison with rapid decompression (RDC), CDC reduced the degree of brain edema, diminished the level of cellular apoptosis and enhanced neurological function, and whereas the neuroprotective effect of CDC could be reversed by rapamycin (Rap). The expressions of Beclin-1 and LC3 in CDC group were significantly lower than those of RDC group, and the expression levels of these two proteins were significantly elevated after the addition of Rap. The expression of p-Akt in CDC group was considerably enhanced than RDC group. After the addition of LY294002, a PI3K/Akt pathway inhibitor, p-Akt protein expression was reduced, and the neuroprotective effect of the rats was markedly inhibited. Taken together, our data demonstrate the superior neuroprotective effect of CDC with regard to alleviating early brain edema, improving the neurological status, suppressing apoptosis and inhibiting neuronal autophagy via triggering PI3K/Akt signaling pathway.

Keywords: Autophagy; Controlled decompression; Early brain injury; PI3K/Akt signaling pathway; Traumatic epidural intracranial hypertension.