Detection of cannabinoid receptor biomarkers and uses thereof
View Patent ↗Traumatic insult to the brain leads to a degradation of low molecular weight of cannabinoid type 1 receptor (CB1) and generation of high molecular weight complexes in the cortex and hippocampus, as assessed by both N-terminal and C-terminal specific antibodies. The formation and release of CB1 oligomers was dramatically increased into CSF within 1 hour following traumatic brain insult. Novel CB1 receptor-based, prognostic markers of traumatic brain injury and other forms of brain injury are disclosed. A method of repopulating damaged neural cells by proliferation of a subgroup of neural progenitor cells is described. Targeting CB1 receptors for therapeutic neuroprotection in TBI is also disclosed.
1. A method for determining the presence of traumatic brain injury (TBI), comprising analyzing for cannabinoid receptor type 1 (CB1) extracellular N-terminal and C-terminal biomarker proteins selected from the group consisting of 40-42 kDa, 62-64 kDa, 120-130 kDa, and >260 kDa monomeric or multimeric CB1 complexes in a cerebral spinal fluid (CSF), hippocampal, cortical or serum sample from a subject suspected of having TBI within and up to about 14 days from the TBI; and
comparing levels of the biomarker proteins in a comparable sample from a normal subject;
wherein levels of extracellular N-terminal biomarker CB1 proteins are decreased and levels of the C-terminal biomarker CB1 proteins are increased in the sample of the subject suspected of having TBI compared to comparable samples from normal subjects.
2. The method of claim 1 , wherein the 120-130 kDa protein biomarker levels are decreased within 3 hours of TBI in the TBI subject.
3. The method of claim 1 , wherein accumulation of high molecular weight CB1 C-terminal domain molecular weight levels of oligomers with kDa greater than 260 in the sample from the subject suspected of having TBI compared to oligomer levels in a normal subject is indicative of TBI.
4. The method of claim 3 , wherein the oligomers with molecular weights greater than 260 kDa accumulate within 3 hours of TBI.
5. The method of claim 1 , wherein high molecular weight CB1 C-terminal domain oligomers greater than 260 kDa accumulate within one hour of TBI with a gradual decline up to 14 days post injury in the subject having TBI compared to levels of the oligomers in normal subjects.
6. The method of claim 1 , wherein TBI is indicated by a decrease in N-terminal staining and an increase in C-terminal staining of the CB1 complexes in cortex or hippocampus tissue samples compared to staining in a comparable sample from a normal subject.
7. The method of claim 1 , wherein the analyzing is with N-terminal and C-terminal specific CB1 antibodies.
8. The method of claim 1 , wherein the sample is cerebrospinal fluid (CSF), cortex tissue or hippocampus tissue.
9. The method of claim 8 , wherein the tissue sample is brain cortex or hippocampus.
10. The method of claim 8 , wherein the sample is CSF.
11. The method of claim 1 , wherein the sample is blood.