Abstract
Traumatic brain injury (TBI) is one of the major health problems worldwide that causes death or permanent disability through primary and secondary damages in the brain. TBI causes primary brain damage and activates glial cells and immune and inflammatory cells, including mast cells in the brain associated with neuroinflammatory responses that cause secondary brain damage. Though the survival rate and the neurological deficiencies have shown significant improvement in many TBI patients with newer therapeutic options, the underlying pathophysiology of TBI-mediated neuroinflammation, neurodegeneration, and cognitive dysfunctions is understudied. In this study, we analyzed mast cells and neuroinflammation in weight drop-induced TBI. We analyzed mast cell activation by toluidine blue staining, serum chemokine C-C motif ligand 2 (CCL2) level by enzyme-linked immunosorbent assay (ELISA), and proteinase-activated receptor-2 (PAR-2), a mast cell and inflammation-associated protein, vascular endothelial growth factor receptor 2 (VEGFR2), and blood-brain barrier tight junction-associated claudin 5 and Zonula occludens-1 (ZO-1) protein expression in the brains of TBI mice. Mast cell activation and its numbers increased in the brains of 24 h and 72 h TBI when compared with sham control brains without TBI. Mouse brains after TBI show increased CCL2, PAR-2, and VEGFR2 expression and derangement of claudin 5 and ZO-1 expression as compared with sham control brains. TBI can cause mast cell activation, neuroinflammation, and derangement of tight junction proteins associated with increased BBB permeability. We suggest that inhibition of mast cell activation can suppress neuroimmune responses and glial cell activation-associated neuroinflammation and neurodegeneration in TBI.
Highlights
Acquired brain injury may be due to traumatic or nontraumatic injury
We report increased mast cell activation and upregulated C-C motif ligand 2 (CCL2), proteinase-activated receptor-2 (PAR-2), and vascular endothelial growth factor receptor 2 (VEGFR2) expression along with the reduced levels of claudin 5 and Zonula occludens-1 (ZO-1) in mouse Traumatic brain injury (TBI) brains
Representative microphotograph shows an increased number of astrocyte activation as determined by Glial Fibrillary Acidic Protein (GFAP) immunostaining for astrocytes in TBI mice (72 h) as compared to sham control mice (Figure 1(c))
Summary
Acquired brain injury may be due to traumatic or nontraumatic injury. Traumatic brain injury (TBI) is “an alteration in brain function or other evidence of brain pathology caused by an external force (open/penetrating or closed/nonpenetrating) (Brain Injury Association of America, Vienna, VA, USA).” TBI may be due to falls, assaults, vehicle accidents, sports activity-related injuries, head trauma, gunshots, jobrelated injuries, child abuse, domestic violence, military activities including blasts, etc. Traumatic brain injury (TBI) is “an alteration in brain function or other evidence of brain pathology caused by an external force (open/penetrating or closed/nonpenetrating) (Brain Injury Association of America, Vienna, VA, USA).”. The secondary brain injury is due to the neuroimmune and inflammatory response to TBI [2]. The severity of a TBI pathogenesis may range from “mild” with a slight change in mental status or consciousness to “severe” with unconsciousness or amnesia after the brain injury. The acute and chronic effects of brain injuries vary significantly from person to person or in animal models of TBI [3, 4]. No two TBIs are the same with reference to the neuroimmune response and disease severity. The current therapeutic options significantly improve the survival rate and the neurological deficiencies, the underlying molecular and immunological mechanism of TBI is still largely unknown [6, 7]
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