Microtubule-Associated Protein 2 Levels Decrease in Hippocampus Following Traumatic Brain Injury

Abstract

We examined microtubule-associated protein 2 (MAP2) levels in hippocampal and cortical tissue 3 h following moderate traumatic brain injury (TBI) in the rat. MAP2 levels were assayed by quantitative immunoreactivity in tissue fractions obtained from naive, sham-injured, or fluid percussion-injured animals. Tissues were homogenized in the presence of protease inhibitors (0.3 mM phenylmethylsulfonyl fluoride, PMSF), a specific calpain inhibitors (0.1 mM leupeptin), and chelators (2 mM ethylene glycol-bis-tetraacetic acid, EGTA; 1 mM ethylenedinitrilo-tetraacetic acid, EDTA) to eliminate in vitro MAP2 proteolysis during tissue processing. Compared to naive rats, sham injury had no effect on soluble MAP2 levels in either cortex (105.0 +/- 4.4% of naive value) or hippocampus (106.6 +/- 5.2% of naive value). However, TBI caused a significant (p < 0.005) decrease in hippocampal MAP2 levels (55.7 +/- 5.9% of sham-injured controls). The effect appeared to be regionally selective, since the MAP2 decrease did not occur in cortex (89.1 +/- 1.4%). The degree of MAP2 decrease in hippocampus was similar in both membrane (57.8%) and cytosolic (55.7%) fractions, ruling out the possibility of partitioning artifacts. The data suggest that sublethal alterations of neuronal structure and function caused by MAP2 degradation may play an important role in the development of TBI-induced functional deficits. Since MAP2 is exclusively associated with the cytoskeleton in somal and dendritic compartments of neurons, the pathophysiology of sublethal magnitudes of TBI may also involve dendritic and somal dysfunction.

Rapid Calpain I Activation and Cytoskeletal Protein Degradation Following Traumatic Spinal Cord Injury: Attenuation with Riluzole Pretreatment

“…Magnification bar equals 100 tim. Taft et al, 1992;Roberts-Lewis and Siman, 1993;Matesic and Lin, 1994;Roberts-Lewis et al, 1994;Kampfl et al, 1996a,b;Posmantur et al, 1996). Several lines of evidence support the hypothesis that cytoskeletal degradation is extremely sensitive to glutamate-and Ca 2~-mediated excitotoxic events.…”

Hippocampus, amygdala, and basal ganglia morphometrics in children after moderate‐to‐severe traumatic brain injury

“…Others have reported impaired long-term potentiation 24 fluid percussion injury in hippocampal tissue, despite no change in cortical tissue. 25 Additionally, inflammatory processes, such as early intense increased glial fibrillary acidic protein immunoreactivity, 26 upregulation of ß-Amyloid precursor protein, 27,28 alterations in regional metabolism, 29 seizures, 30 as well as hypoxia, ischemia, and hyperemia, 31,32 may further exacerbate injury in the hippocampus.…”

Rapid regulation of microtubule-associated protein 2 in dendrites of nucleus laminaris of the chick following deprivation of afferent activity

“…and adult brain. This idea is supported by dynamic regulation of MAP2 expression and its involvement in dynamic changes in neuronal morphology caused by excitotoxins (Siman and Noszek, 1988;Bigot et al, 1991;Felipo et al, 1993;Arias et al, 1997;Faddis et al, 1997;Hoskison and Shuttleworth, 2006;Hoskison et al, 2007), traumatic brain injury (Taft et al, 1992;Folkerts et al, 1998), or focal ischemia (Pettigrew et al, 1996;Schwab et al, 1998). In addition, manipulations of synaptic activity alter the immunoreactivity for MAP2 in dendrites (Hendry and Bhandari, 1992;Steward and Halpain, 1999;Vaillant et al, 2002), further suggesting that synaptic activity either directly or indirectly regulates MAP2 expression.…”