Abstract
Traumatic brain injury (TBI) can result in persistent sensorimotor and cognitive deficits, which occur through a cascade of deleterious pathophysiological events over time. In this study, we investigated the hypothesis that neurodegeneration caused by TBI leads to impairments in sensorimotor function. TBI induces the activation of the caspase-3 enzyme, which triggers cell apoptosis in an in vivo model of fluid percussion injury (FPI). We analyzed caspase-3 mediated apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and poly (ADP-ribose) polymerase (PARP) and annexin V western blotting. We correlated the neurodegeneration with sensorimotor deficits by conducting the animal behavioral tests including grid walk, balance beam, the inverted screen test, and the climb test. Our study demonstrated that the excess cell death or neurodegeneration correlated with the neuronal dysfunction and sensorimotor impairments associated with TBI.
Highlights
Traumatic brain injury (TBI) is defined as a debilitating effect on brain function resulting from a blunt or penetrating injury to the brain [1,2]
We first analyzed the expression of the cleaved form of caspase-3 after mild (7 psi) and moderate (15 psi) fluid-percussion model of traumatic brain injury (TBI) in mice
We assessed the level of cleaved poly (ADP-ribose) polymerase (PARP) fragment, a marker of apoptosis
Summary
Traumatic brain injury (TBI) is defined as a debilitating effect on brain function resulting from a blunt or penetrating injury to the brain [1,2]. Brain Sci. 2018, 8, 11 oxygen species (ROS) generated by the enzymatic action of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 (NOX1) leads to activation of matrix metalloproteinase-2 (MMP-2) that cleaves stromal cell-derived factor 1α (SDF-1α) to neurotoxic SDF-1 (5–67) fragment and leads to caspase-3 dependent apoptotic cell death [9]. In another recent study, we reported that the NOX1 activation causes upregulation of transforming growth factor-beta 1 (TGF-β1) that leads to caspase-3 mediated apoptosis via the phosphorylation of Smad and Smad proteins. The parameters of apoptotic cell death were found to be upregulated in mice subjected to mild and moderate TBI and were concomitant with the severity of the injury and loss of sensorimotor function
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