Research Paper Volume 13, Issue 12 pp 16088—16104
High glucose exacerbates neuroinflammation and apoptosis at the intermediate stage after post-traumatic brain injury
- 1 Department of Neurosurgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- 2 Hebei Institute of Head Trauma, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- 3 Department of Cardiology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
- 4 Department of Endocrinology, Tangshan Gongren Hospital, Tangshan, Hebei 063000, China
Received: March 1, 2021 Accepted: May 19, 2021 Published: June 27, 2021https://doi.org/10.18632/aging.203136
How to Cite
Copyright: © 2021 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Traumatic brain injury (TBI) is a highly lethal event with a poor prognosis. Recovering residual neuronal function in the intermediate stage of TBI is important for treatment; however, neuroinflammation and neuronal apoptosis impede residual neuronal repair processes. Considering that hyperglycemia influences inflammatory processes and neuronal survival, we examined the effects of high glucose on neuroinflammation and neuronal death during the intermediate phase of TBI. Rat models of type 2 diabetes mellitus and/or TBI were developed and behaviorally assessed. Neurological function and cognitive abilities were impaired in TBI rats and worsened by type 2 diabetes mellitus. Histopathological staining and analyses of serum and hippocampal mRNA and protein levels indicated that neuroinflammation and apoptosis were induced in TBI rats and exacerbated by hyperglycemia. Hyperglycemia inhibited hippocampal mitogen-activated protein kinase kinase 5 (MEK5) phosphorylation in TBI rats. In vitro assays were used to assess inflammatory factor expression, apoptotic protein levels and neuronal survival after MEK5 activation in TBI- and/or high-glucose-treated neurons. MEK5/extracellular signal-regulated kinase 5 (ERK5) pathway activation reduced the inflammation, cleaved caspase-3 expression, Bax/Bcl-2 ratio and apoptosis of TBI neurons, even under high-glucose conditions. Thus, high glucose exacerbated neuroinflammation and apoptosis in the intermediate stage post-TBI by inhibiting the MEK5/ERK5 pathway.