A study published in the Journal of Cannabis Research examined the effect of granulocyte colony-stimulating factor (G-CSF) on brain recovery following traumatic brain injury (TBI). The findings showed that cannabinoid type 2 receptors (CB2R) in the endocannabinoid system (eCB) play a critical role in G-CSF’s promotion of balance and coordination recovery after controlled cortical impact (CCI) injury.
Previous studies have shown that G-CSF treatment after TBI is effective in rodents. G-CSF enhances hippocampal neurogenesis, brain repair, and behavioral recovery. Other studies found that Delta-9 tetrahydrocannabinol (THC) and G-CSF support TBI recovery. This study explored how G-CSF interacts with the endocannabinoid system after CCI. THC treatment is known to promote G-CSF upregulation.
The researchers triggered this activity by administering cannabinoid (CB) receptor antagonists. These antagonists targeted CB1 and CB2 receptors to observe the role of CB2Rs in G-CSF's enhancement of brain repair. CB2-R KO mice sustained CCI to the right frontal cortex. Two control mouse groups received G-CSF. The research team treated the mice for three days after CCI, giving daily subcutaneous injections of G-CSF (100 microg/kg). On day three after CCI, the mice were euthanized. The researchers perfused the brains with heparinized saline and dissected them into three regions: cerebral cortex, corpus striatum, and hippocampus.
Data analysis revealed that the CB2R mice were significantly impaired on the rotometer prior to CCI to the right frontal cortex. This finding suggested that CB2R activity facilitates the normal function of neural networks that mediate balance and coordination.
The researchers noted that CB2R expression increased by G-CSF treatment in normal mice 3 days after CCI, but not in CB2R KO mice. The CB1R in the CB2R KO mice was upregulated by G-CSF treatment. Data analysis suggested lowering expression of CB2R did not impact expression of CB1R. Expression of the neurotrophic factors BDNF and GDNF did not change with G-CSF treatment in CB2R KO mice.
The study found that G-CSF administration for 3 days after CCI did not enhance recovery of balance and coordination measured on the rotometer in CB2R KO mice. The research team observed beneficial effects of G-CSF treatment in normal control mice. The study offers valuable insights into how TBI affects brain cells and highlights important considerations for future research. Additional studies on the effect of CB2R activity can lead to novel therapeutic treatments for patients recovering from CCI.
Source: Journal of Cannabis Research