Journal of neurotrauma
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Journal of neurotrauma · Oct 2012
Acetylcholinesterase inhibition interacts with training to reverse spatial learning deficits after cortical impact injury.
Cholinergic mechanisms are known to play a key role in cognitive functions that are profoundly altered in traumatic brain injury (TBI). The present investigation was designed to test the ability of continuous administration, starting at the time of injury, of physostigmine (PHY), an acetylcholinesterase (AChE) inhibitor that crosses the blood-brain barrier (BBB), to ameliorate the alterations of learning and memory induced by cerebral cortex impact injury in rats under isoflurane anesthesia. Learning and memory were assessed with the Morris water maze implemented during days 7-11 (WM1), and days 21-25 post-TBI (WM2), with four trials per day for 3 days, followed by target reversal and 2 additional days of training. ⋯ In WM2 tests, PHY improved within- and between-sessions performance at both dose levels. We found that continuous AChE inhibition interacted with repeated training on the water maze task to completely reverse the deficits seen in learning and memory induced by TBI. The PHY treatment also reduced the amount of brain tissue loss as measured using cresyl violet staining.
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In order to quantify degenerative and regenerative changes and analyze the contribution of multiple factors to the outcome after neurite transection, we cultured adult mouse dorsal root ganglion neurons, and with a precise laser beam, we transected the nerve fibers they extended. Cell preparations were continuously visualized for 24 h with time-lapse microscopy. More distal cuts caused a more elongated field of degeneration, while thicker neurites degenerated faster than thinner ones. ⋯ Branching slowed the regenerative process, while simultaneous degeneration of uncut neurites increased it. Proximal lesions, small neuronal size, and extensive and rapid neurite degeneration were predictive of death of an injured neuron, which typically displayed necrotic rather than apoptotic form. In conclusion, this in vitro model proved useful in unmasking many new aspects and correlates of mechanically-induced neurite injury.
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Journal of neurotrauma · Oct 2012
A discrimination task used as a novel method of testing decision-making behavior following traumatic brain injury.
Traumatic brain injury (TBI) results in a multitude of deficits following injury. Some of the most pervasive in humans are the changes that affect frontally-mediated cognitive functioning, such as decision making. The assessment of decision-making behavior in rodents has been extensively tested in the field of the experimental analysis of behavior. ⋯ Upon reaching criterion, a reversal discrimination was evaluated in which the reinforcer was placed in unscented sand. Finally, a novel scent discrimination (basil versus coffee with basil reinforced), and a reversal (coffee) were evaluated. The results indicated that the Dig task is a simple experimental preparation that can be used to assess deficits in decision-making behavior following TBI.
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Journal of neurotrauma · Sep 2012
Involvement of mitogen-activated protein kinase pathways in expression of the water channel protein aquaporin-4 after ischemia in rat cortical astrocytes.
Brain edema after ischemic brain injury is a key determinant of morbidity and mortality. Aquaporin-4 (AQP4) plays an important role in water transport in the central nervous system and is highly expressed in brain astrocytes. However, the AQP4 regulatory mechanisms are poorly understood. ⋯ Treatment with SB203580, a selective p38 MAPK inhibitor, or SP600125, a selective c-Jun N-terminal kinase inhibitor, significantly attenuated the return of AQP4 to its normal level, and SB203580, but not SP600125, significantly decreased cell death. In an in vivo study, AQP4 expression was upregulated 1-3 days after reperfusion, which was consistent with the time course of p38 phosphorylation and activation, and decreased by the p38 inhibition after transient middle cerebral artery occlusion (MCAO). These results suggest that p38 MAPK may regulate AQP4 expression in cortical astrocytes after ischemic injury.