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Published on: June 11, 2017
Early increase of cannabinoid receptor density after experimental traumatic brain injury in the newborn piglet
Cornelius K Donat1, Felix Fischer, Bernd Walter
1Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig, Germany, cdonat@nru.dk.
Insights
Paediatric traumatic brain injury (TBI) shows altered cannabinoid receptor (CBR) binding. Specifically, CB2R density increased, suggesting a neuroprotective mechanism in TBI recovery.
Area of Science:
- Neuroscience
- Pharmacology
- Paediatric Medicine
Background:
- Traumatic brain injury (TBI) in children is a major cause of death and disability.
- Cannabinoid mechanisms have shown neuroprotective effects after TBI, implicating cannabinoid receptors (CBRs).
Purpose of the Study:
- To determine cannabinoid receptor (CBR) densities and translocator protein 18 kDa (TSPO) expression in newborn piglets following experimental TBI.
- To investigate the role of CBRs in the early stages of paediatric TBI.
Main Methods:
- Newborn piglets underwent sham operation or fluid-percussion (FP) injury.
- Brain tissue was analyzed 6 hours post-injury using radioligands for CBRs ([3H]CP-55,940, [3H]SR141716A) and TSPO ([3H]PK11195).
- Physiological parameters including ICP, CPP, CBF, and CMRO2 were monitored.
Main Results:
- FP-TBI caused increased ICP and temporarily reduced CPP, but CBF and CMRO2 remained physiological.
- A significant increase in [3H]CP-55,940 binding was observed in 15 of 24 brain regions post-TBI.
- No significant changes in [3H]SR141716A (CB1R-selective) binding were detected.
- A trend towards increased [3H]PK11195 binding suggested incipient microglial activation.
Conclusions:
- The increased [3H]CP-55,940 binding reflects changes in CB2R density, not CB1R, in this paediatric TBI model.
- These findings may explain the neuroprotective effects of cannabinoid ligands.
- The results offer insights for future therapeutic strategies for TBI.
Abstract:
Paediatric traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies showed neuroprotection after TBI by (endo)cannabinoid mechanisms, suggesting involvement of cannabinoid receptors (CBR). We therefore determined CBR densities and expression of the translocator protein 18 kDA (TSPO) in newborn piglets after experimental TBI. Newborn female piglets were subjected to sham operation (n=6) or fluid-percussion (FP) injury (n=7) under controlled physiological conditions. After six hours, brains were frozen, sagittally cut and incubated with radioligands for CBR ([3HCP-55,940, [3H]SR141716A) and TSPO ([3H]PK11195), an indicator of gliosis/brain injury. Early after injury, FP-TBI elicited a significant ICP increase at a temporary reduced cerebral perfusion pressure; however, CBF and CMRO2 remained within physiological range. At 6 hours post injury, we found a statistically significant increase in binding of the non-selective agonist [3H]CP-55,940 in 15 of the 24 investigated brain regions of injured animals. By contrast, no significant changes in binding of the CB1R-selective antagonist [3H]SR141716A were observed. A non-significant trend towards increased binding of [3H]PK11195 was observed, suggesting an incipient microglial activation. We therefore conclude that in this model and time span after injury, the increase in [3H]CP-55,940 binding reflects changes in CB2R density, while CB1R density is not affected. The results may provide explanation for the neuroprotective properties of cannabinoid ligands and future therapeutic strategies of TBI.
