Category Archives: Brain Trauma

Co-localization of the cannabinoid type 1 receptor with corticotropin-releasing factor-containing afferents in the noradrenergic nucleus locus coeruleus: implications for the cognitive limb of the stress response.

Posted on by
Reply

Image result for Brain Structure and Function journal

“The noradrenergic system has been shown to play a key role in the regulation of stress responses, arousal, mood, and emotional states. Corticotropin-releasing factor (CRF) is a primary mediator of stress-induced activation of noradrenergic neurons in the nucleus locus coeruleus (LC).

The endocannabinoid (eCB) system also plays a key role in modulating stress responses, acting as an “anti-stress” neuro-mediator.

In the present study, we investigated the cellular sites for interactions between the cannabinoid receptor type 1 (CB1r) and CRF in the LC.

Taken together, these results indicate that the eCB system is poised to directly modulate stress-integrative heterogeneous CRF afferents in the LC, some of which arise from limbic sources.”

 https://www.ncbi.nlm.nih.gov/pubmed/28255675

CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.

Posted on by
Reply

Image result for european neuropsychopharmacology

“The role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved.

The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved.

Our results indicate that CB2R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia.”

https://www.ncbi.nlm.nih.gov/pubmed/28253997

Endocannabinoid 2-arachidonoylglycerol protects inflammatory insults from sulfur dioxide inhalation via cannabinoid receptors in the brain.

Posted on by
Reply

Image result for J Environ Sci (China).

“Sulfur dioxide (SO2) pollution in the atmospheric environment causes brain inflammatory insult and inflammatory-related microvasculature dysfunction. However, there are currently no effective medications targeting the harmful outcomes from chemical inhalation.

Endocannabinoids (eCBs) are involved in neuronal protection against inflammation-induced neuronal injury. The 2-arachidonoylglycerol (2-AG), the most abundant eCBs and a full agonist for cannabinoid receptors (CB1 and CB2), is also capable of suppressing proinflammatory stimuli and improving microvasculature dysfunction.

Here, we indicated that endogenous 2-AG protected against neuroinflammation in response to SO2 inhalation by inhibiting the activation of microglia and astrocytes and attenuating the overexpression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-a), interleukin (IL)-1β, and inducible nitric oxide synthase (iNOS).

In addition, endogenous 2-AG prevented cerebral vasculature dysfunction following SO2 inhalation by inhibiting endothelin 1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) expression, elevating endothelial nitric oxide synthase (eNOS) level, and restoring the imbalance between thromboxane A2 (TXA2) and prostaglandin I2 (PGI2).

In addition, the action of endogenous 2-AG on the suppression of inflammatory insult and inflammatory-related microvasculature dysfunction appeared to be mainly mediated by CB1 and CB2 receptors.

Our results provided a mechanistic basis for the development of new therapeutic approaches for protecting brain injuries from SO2 inhalation.”

https://www.ncbi.nlm.nih.gov/pubmed/28115138

Neuroimmmune interactions of cannabinoids in neurogenesis: focus on interleukin-1β (IL-1β) signalling.

Posted on by
Reply

Biochemical Society Transactions

“Neuroimmune networks and the brain endocannabinoid system contribute to the maintenance of neurogenesis.

Activation of cannabinoid receptors suppresses chronic inflammatory responses through the attenuation of pro-inflammatory mediators. Moreover, the endocannabinoid system directs cell fate specification of NSCs (neural stem cells) in the CNS (central nervous system).

The aim of our work is to understand better the relationship between the endocannabinoid and the IL-1β (interleukin-1β) associated signalling pathways and NSC biology, in order to develop therapeutical strategies on CNS diseases that may facilitate brain repair.

NSCs express functional CB1 and CB2 cannabinoid receptors, DAGLα (diacylglycerol lipase α) and the NSC markers SOX-2 and nestin. We have investigated the role of CB1 and CB2 cannabinoid receptors in the control of NSC proliferation and in the release of immunomodulators [IL-1β and IL-1Ra (IL-1 receptor antagonist)] that control NSC fate decisions. Pharmacological blockade of CB1 and/or CB2 cannabinoid receptors abolish or decrease NSC proliferation, indicating a critical role for both CB1 and CB2 receptors in the proliferation of NSC via IL-1 signalling pathways.

Thus the endocannabinoid system, which has neuroprotective and immunomodulatory actions mediated by IL-1 signalling cascades in the brain, could assist the process of proliferation and differentiation of embryonic or adult NSCs, and this may be of therapeutic interest in the emerging field of brain repair.

In summary, cannabinoids and IL-1β seem to play antagonistic roles in neurogenesis: although cannabinoids increase proliferation and induce formation and maturation of new neurons, IL-1β blocks proliferation and formation of new neurons, inducing a shift towards a glial fate. This may be important in situations such as in aging, neurodegenerative diseases, and lesions of the brain and spinal cord.”

http://www.biochemsoctrans.org/content/41/6/1577.long

Endogenous cannabinoid system alterations and their role in epileptogenesis after brain injury in rat.

Posted on by
Reply

Image result for epilepsy research journal

“Post-traumatic epilepsy (PTE) is one of the most common complications resulting from brain injury, however, antiepileptic drugs usually fail to prevent it.

Several lines of evidence have demonstrated that the endogenous cannabinoid system (ECS) plays a pivotal role during epileptogenesis in several animal models.

A recent study has shown that a cannabinoid type 1 (CB1) receptor antagonist could suppress long-term neuron hyperexcitability after brain injury, but the underlying mechanisms remain largely unknown.

In this study, we first analyzed the dynamic expression of different components of the ECS at various time points after brain injury in rats. Then, we conducted a 12-month-long session of behavioral monitoring after the brain injury, and based on the results, the rats were divided into a PTE group and a non-PTE group. Finally, the changes in the ECS between the two groups were compared.

We found that the ECS exhibited a biphasic alteration after brain injury; the expression of the CB1 receptor and 2-arachidonoylglycerol (2-AG) in the PTE group was significantly higher than that of the non-PTE group 12 months after traumatic brain injury.

Our preliminary results indicated that the ECS might be involved in post-traumatic epileptogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27810514

Mild Traumatic Brain Injury Produces Neuron Loss That Can Be Rescued by Modulating Microglial Activation Using a CB2 Receptor Inverse Agonist.

Posted on by
Reply

Image result for Front Neurosci.

“We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits.

We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using 2-week daily administration of the CB2 inverse agonist SMM-189.

Overall, our findings indicate that SMM-189 rescues damaged neurons and thereby alleviates functional deficits resulting from TBI, apparently by selectively modulating microglia to the beneficial M2 state.

CB2 inverse agonists thus represent a promising therapeutic approach for mitigating neuroinflammation and neurodegeneration.”

 https://www.ncbi.nlm.nih.gov/pubmed/27766068

Neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol in hypoxic-ischemic newborn piglets.

Posted on by
Reply

Image result for Pediatr Res.

“To test the neuroprotective effects of the nonpsychoactive cannabinoid cannabidiol (CBD), piglets received i.v. CBD or vehicle after hypoxia-ischemia (HI: temporary occlusion of both carotid arteries plus hypoxia).

CBD administration was free from side effects; moreover, CBD administration was associated with cardiac, hemodynamic, and ventilatory beneficial effects.

In conclusion, administration of CBD after HI reduced short-term brain damage and was associated with extracerebral benefits.”

https://www.ncbi.nlm.nih.gov/pubmed/18679164

Cannabidiol reduces brain damage and improves functional recovery after acute hypoxia-ischemia in newborn pigs.

Posted on by
Reply

Image result for Pediatr Res.

“Newborn piglets exposed to acute hypoxia-ischemia (HI) received i.v. cannabidiol (HI + CBD) or vehicle (HI + VEH). In HI + VEH, 72 h post-HI brain activity as assessed by amplitude-integrated EEG (aEEG) had only recovered to 42 ± 9% of baseline, near-infrared spectroscopy (NIRS) parameters remained lower than normal, and neurobehavioral performance was abnormal (27.8 ± 2.3 points, normal 36). In the brain, there were fewer normal and more pyknotic neurons, while astrocytes were less numerous and swollen. Cerebrospinal fluid concentration of neuronal-specific enolase (NSE) and S100β protein and brain tissue percentage of TNFα(+) cells were all higher. In contrast, in HI + CBD, aEEG had recovered to 86 ± 5%, NIRS parameters increased, and the neurobehavioral score normalized (34.3 ± 1.4 points). HI induced histological changes, and NSE and S100β concentration and TNFα(+) cell increases were suppressed by CBD. In conclusion, post-HI administration of CBD protects neurons and astrocytes, leading to histological, functional, biochemical, and neurobehavioral improvements.”

https://www.ncbi.nlm.nih.gov/pubmed/21654550

Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function.

Posted on by
Reply

Image result for neuropharmacology journal

“Cannabidiol (CBD) demonstrated short-term neuroprotective effects in the immature brain following hypoxia-ischemia (HI).

We examined whether CBD neuroprotection is sustained over a prolonged period.

In conclusion, CBD administration after HI injury to newborn rats led to long-lasting neuroprotection, with the overall effect of promoting greater functional rather than histological recovery.

These effects of CBD were not associated with any side effects.

These results emphasize the interest in CBD as a neuroprotective agent for neonatal HI.”

https://www.ncbi.nlm.nih.gov/pubmed/22659086

Neuroprotective Effects of Cannabidiol In Hypoxic Ischemic Insult: The Therapeutic Window In Newborn Mice.

Posted on by
Reply

Image result for CNS Neurol Disord Drug Targets

“A relevant therapeutic time window (TTW) is an important criterion for considering the clinical relevance of a substance preventing newborn hypoxic-ischemic (HI) brain damage.

OBJECTIVE:

to test the TTW of the neuroprotective effects of cannabidol (CBD), a non-psychoactive cannabinoid in a model of newborn HI brain damage.

RESULTS:

CBD administered up to 18 h after HI reduced IHVL and neuropathological score by 60%, TUNEL+ count by 90% and astrocyte damage by 50%. In addition, CBD blunted the HI-induced increase in microglial population. When CBD administration was delayed 24 h, however, the neuroprotective effect was lost in terms of IHVL, apoptosis or astrogliosis reduction.

CONCLUSION:

CBD shows a TTW of 18 h when administered to HI newborn mice, which represents a broader TTW than reported for other neuroprotective treatments including hypothermia.”

https://www.ncbi.nlm.nih.gov/pubmed/27686886