Related Experiment Video
Updated: Nov 9, 2025
Controlled Cortical Impact Model for Traumatic Brain Injury
Published on: August 5, 2014
Massive efflux of adenosine triphosphate into the extracellular space immediately after experimental traumatic brain
Nobuhiro Moro1,2, Sima S Ghavim1, Richard L Sutton1
1Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine, University of California, LA 90095-6901, USA.
Abstract:
The aim of the current study was to determine effects of mild traumatic brain injury (TBI), with or without blockade of purinergic ATP Y1 (P2Y1) receptors or store-operated calcium channels, on extracellular levels of ATP, glutamate, glucose and lactate. Concentrations of ATP, glutamate, glucose and lactate were measured in cerebral microdialysis samples obtained from the ipsilateral cortex and underlying hippocampus of rats with mild unilateral controlled cortical impact (CCI) or sham injury. Immediately after CCI, a large release of ATP was observed in the cortex (3.53-fold increase of pre-injury value) and hippocampus (2.97-fold increase of pre-injury value), with ATP returning to the baseline levels within 20 min post-injury and remaining stable for during the 3-h sampling period. In agreement with the results of previous studies, there was a significant increase in glutamate 20 min after CCI, which was concomitant with a decrease in extracellular glucose (20 min) and an increase in lactate (40-60 min) in both brain regions after CCI. Addition of a selective P2Y1 receptor blocker (MRS2179 ammonium salt hydrate) to the microdialysis perfusate significantly lowered pre-injury ATP and glutamate levels, and eliminated the post-CCI peaks. Addition of a blocker of store-operated calcium channels [2-aminoethoxy diphenylborinate (2-APB)] to the microdialysis perfusate significantly lowered pre-injury ATP in the hippocampus, and attenuated the post-CCI peak in both the cortex and hippocampus. 2-APB treatment significantly increased baseline glutamate levels, but the values post-injury did not differ from those in the sham group. Pre-injury glucose levels, but not lactate levels, were increased by MRS2179 and decreased by 2-APB. However, none of these treatments substantially altered the CCI-induced reduction in glucose and increase in lactate in the cortex. In conclusion, the results of the present study demonstrated that a short although extensive release of ATP immediately after experimental TBI can be significantly attenuated by blockade of P2Y1 receptors or store-operated calcium channels.
Insights
Mild traumatic brain injury (TBI) causes a rapid release of ATP. Blocking P2Y1 receptors or calcium channels can significantly reduce this ATP release after TBI.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Mild traumatic brain injury (TBI) can lead to significant changes in brain chemistry.
- Extracellular ATP and glutamate play crucial roles in neuronal function and injury response.
Purpose of the Study:
- To investigate the effects of blocking purinergic ATP Y1 (P2Y1) receptors or store-operated calcium channels on extracellular ATP, glutamate, glucose, and lactate levels following mild TBI.
- To understand the role of these pathways in the immediate biochemical cascade after TBI.
Main Methods:
- Controlled cortical impact (CCI) model of mild TBI in rats.
- Cerebral microdialysis to measure extracellular concentrations of ATP, glutamate, glucose, and lactate in the cortex and hippocampus.
- Administration of a selective P2Y1 receptor blocker (MRS2179) and a store-operated calcium channel blocker (2-APB).
Main Results:
- CCI induced a rapid and significant increase in extracellular ATP in both cortex and hippocampus, returning to baseline within 20 minutes.
- Glutamate levels increased, while glucose decreased and lactate increased post-CCI.
- Blockade of P2Y1 receptors or store-operated calcium channels attenuated the post-CCI ATP peaks.
- 2-APB also affected baseline ATP and glutamate levels and attenuated post-CCI ATP peaks.
Conclusions:
- A transient, substantial release of ATP occurs immediately after experimental TBI.
- Blockade of P2Y1 receptors or store-operated calcium channels can significantly attenuate this immediate ATP release.
- These findings suggest potential therapeutic targets for mitigating early biochemical changes after TBI.
