Attenuation of microtubule associated protein-2 degradation after mild head injury by mexiletine and calpain-2 inhibitor

Abstract

The objective of the study was to address the early effects of mild, closed, head injuries on neuronal stability and the prevention of microtubule-associated protein-2 (MAP-2) degradation by mexiletine and calpain-2 inhibitor. Twenty-four rats were divided into four groups: control group (1); trauma group without treatment (2); mexiletine-pretreated and subjected to trauma group (3); trauma subjected and then calpain-2 inhibitor received group (4). All animals were subjected to mild, closed, head trauma. Frontal lobes were removed and processed for staining and immunofluorescent labelling of MAP-2 cytoskeletal proteins, which were evaluated by confocal microscopy in serial optical sections showing the three dimensional cytoarchitecture of affected areas. MAP-2 decoration in almost all neurons obtained from traumatized brain regions drastically diminished, while minute filamentous and granular profiles in axons and/or dendrites were retained together implying a massive degradation/depolymerization of microtubules. In contrast, in mexiletine-pretreated animals, MAP-2 positivity in axonal and perikaryonal profiles was fairly retained, which clearly depicts the protective role of mexiletine after trauma. Compared with mexiletine-pretreated group, calpain-2 inhibitor treated group displayed a less well-preserved MAP-2 expression. Mexiletine can prevent cytoskeletal structure and protein degradation after mild head trauma. Calpain-2 inhibitor prevents protein degradation, but cytoskeletal organization is better preserved with mexiletine.

Calpain-mediated cleavage of collapsin response mediator protein-2 drives acute axonal degeneration

“…To identify functionally relevant downstream molecular targets of calpain activation during AAD, we evaluated the expression levels of different proteins that had previously been reported to be cleaved by calpain in other model systems232425262728. Based on previous studies of our group and others110, we focused on proteins that are involved in autophagy, cytoskeleton integrity and axonal transport as these processes are pivotal for axonal degeneration.…”

Progesterone and vitamin D: Improvement after traumatic brain injury in middle-aged rats

“…Therefore, MAP-2 immunostaining has been widely applied to label the dendritic meshwork and to estimate the dynamic changes in dendritic architecture. Previous studies have shown that MAP-2 degeneration is related to lipid peroxidation and calcium-related calpain activation (Ercan et al, 2001; Atalay et al, 2007). PROG is protective against excitotoxicity by reducing N-methyl-D-aspartate (NMDA), glutamate and excitatory cholinergic signaling, and by balancing Ca 2+ mobilization (Cai et al, 2008; Hu et al, 2009).…”

Neuroproteomics and systems biology‐based discovery of protein biomarkers for traumatic brain injury and clinical validation

“…The most well-studied nonproprietary potential biomarkers for TBI and stroke include S-100b [55][56][57][58][59][60][61] neuron-specific enolase (NSE) [62][63][64][65], glial fibrillary acidic protein (GFAP) [66][67][68], and SBDPs [69][70][71][72][73]. More recent studies in TBI biomarkers include, UCH-L1, MAP-2, and TAU proteins [47,74,75]. Below is the description of the major identified putative biomarkers in the area of TBI.…”