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Lateral Fluid Percussion: Model of Traumatic Brain Injury in Mice
Published on: August 22, 2011
Subtle alterations in NMDA-stimulated cyclic GMP levels following lateral fluid percussion brain injury
M D Temple1, T M Delahunty, R J Hamm
1Department of Psychology, Medical College of Virginia/Virginia Commonwealth University, Richmond, USA.
Abstract:
This study examined whether NMDA-stimulated cyclic GMP levels were altered at two different time points following lateral fluid percussion injury. At 60 min and 15 days postinjury, the left and right hippocampi were dissected and chopped into mini-prisms. Each hippocampus was divided into five equal parts and incubated with either the phosphodiesterase inhibitor IBMX (3-isobutyl-1-methylxanthine, 500 microM) alone, IBMX and N-methyl-D-aspartic acid (NMDA) OR IBMX, NMDA, and glycine (10 MM). Two concentrations of NMDA were used: 500 or 1,000 microM. Tissues were then assayed for levels of cyclic GMP. Results indicated that there were no changes in basal levels of cyclic GMP at either postinjury time point. At 60 min postinjury, there were no significant main effects for injury or drug concentration. There was a significant injury x side interaction effect with increased levels of NMDA-stimulated cyclic GMP in the hippocampus ipsilateral to the injury impact and decreased cyclic GMP levels in the contralateral hippocampus. There were no significant alterations in NMDA-stimulated cyclic GMP levels at 15 days postinjury. The data from this study indicated that NMDA-stimulated cyclic GMP accumulation is differentially altered in the hippocampus ipsilateral and contralateral to the site of the injury at 1 h after injury, but is normalized by 15 days postinjury. These findings implicate NMDA-mediated intracellular signaling processes in the acute excitotoxic response to injury.
Insights
Traumatic brain injury alters N-methyl-D-aspartic acid (NMDA)-stimulated cyclic GMP levels in the hippocampus shortly after injury, with levels returning to normal by 15 days post-injury. This suggests NMDA signaling is involved in the acute response to brain trauma.
Area of Science:
- Neuroscience
- Neurobiology
- Biochemistry
Background:
- Traumatic brain injury (TBI) can lead to complex cellular and molecular changes in the brain.
- The N-methyl-D-aspartic acid (NMDA) receptor pathway plays a critical role in synaptic plasticity and excitotoxicity.
- Cyclic GMP (cGMP) is a second messenger involved in various cellular signaling pathways, including those modulated by NMDA receptors.
Purpose of the Study:
- To investigate the impact of lateral fluid percussion injury on NMDA-stimulated cyclic GMP (cGMP) levels in the hippocampus.
- To determine if alterations in NMDA-stimulated cGMP levels are time-dependent following TBI.
Main Methods:
- Hippocampal tissue from rats subjected to lateral fluid percussion injury was collected at 60 minutes and 15 days post-injury.
- Tissue mini-prisms were incubated with IBMX (a phosphodiesterase inhibitor) and varying concentrations of NMDA, with or without glycine.
- Cyclic GMP levels were measured using biochemical assays.
Main Results:
- Basal cGMP levels showed no significant changes at either time point post-injury.
- At 60 minutes post-injury, NMDA-stimulated cGMP levels were significantly increased in the hippocampus ipsilateral to the injury and decreased in the contralateral hippocampus.
- No significant alterations in NMDA-stimulated cGMP levels were observed at 15 days post-injury.
Conclusions:
- NMDA-stimulated cGMP accumulation is acutely and differentially affected in hippocampal regions ipsilateral and contralateral to the injury site.
- These changes in NMDA-mediated signaling are normalized by 15 days post-injury.
- The findings implicate NMDA receptor-mediated intracellular signaling in the acute excitotoxic response following TBI.
