Stroke / Traumatic Brain Injury Information: Stroke Recovery and Medical Marijuana
A stroke is a medical emergency. Strokes happen when blood flow to your brain stops. Within minutes, brain cells begin to die. There are two kinds of stroke. The more common kind, called ischemic stroke, is caused by a blood clot that blocks or plugs a blood vessel in the brain.
Recent years have brought a wealth of new scientific understanding regarding how medical marijuana or cannabis can be beneficial for treating Stroke / Traumatic Brain Injury.
The other kind, called hemorrhagic stroke, is caused by a blood vessel that breaks and bleeds into the brain. “Mini-strokes” or transient ischemic attacks (TIAs), occur when the blood supply to the brain is briefly interrupted.
Symptoms of stroke are:
- Sudden numbness or weakness of the face, arm or leg (especially on one side of the body)
- Sudden confusion, trouble speaking or understanding speech
- Sudden trouble seeing in one or both eyes
- Sudden trouble walking, dizziness, loss of balance or coordination
- Sudden severe headache with no known cause
If you have any of these symptoms, you must get to a hospital quickly to begin treatment. Acute stroke therapies try to stop a stroke while it is happening by quickly dissolving the blood clot or by stopping the bleeding. Post-stroke rehabilitation helps individuals overcome disabilities that result from stroke damage. Drug therapy with blood thinners is the most common treatment for stroke.
Cannabidiol administration after hypoxia-ischemia to newborn rats reduces long-term brain injury and restores neurobehavioral function.
- Experimental Unit, Foundation for Biomedical Research, Madrid, Spain.
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. Newborn Wistar rats underwent HI injury (10% oxygen for 120 min after left carotid artery electrocoagulation) and then received vehicle (HV, n = 22) or 1 mg/kg CBD (HC, n = 23). Sham animals were similarly treated (SV, n = 16 and SC, n = 16). The extent of brain damage was determined by magnetic resonance imaging, histological evaluation (neuropathological score, 0-5), magnetic resonance spectroscopy and Western blotting. Several neurobehavioral tests (RotaRod, cylinder rear test[CRT],and novel object recognition[NOR]) were carried out 30 days after HI (P37). CBD modulated brain excitotoxicity, oxidative stress and inflammation seven days after HI. We observed that HI led to long-lasting functional impairment, as observed in all neurobehavioral tests at P37, whereas the results of HC animals were similar to those of sham animals (all p < 0.05 vs. HV). CBD reduced brain infarct volume by 17% (p < 0.05) and lessened the extent of histological damage. No differences were observed between the SV and SC groups in any of the experiments. 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.
Cannabidiol prevents infarction via the non-CB1 cannabinoid receptor mechanism.
- Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka City, Fukuoka, 814-0180, Japan.
Cannabidiol, a non-psychoactive constituent of cannabis, has been reported as a neuroprotectant. Cannabidiol and Delta(9)-tetrahydrocannabinol, the primary psychoactive constituent of cannabis, significantly decreased the infarct volume at 4 h in the mouse middle cerebral artery occlusion model. The neuroprotective effects of Delta(9)-tetrahydrocannabinol but not cannabidiol were inhibited by SR141716, a cannabinoid CB1 receptor antagonist, and were abolished by warming of the animals to the levels observed in the controls. Delta(9)-Tetrahydrocannabinol significantly decreased the rectal temperature, and the hypothermic effect was inhibited by SR141716. These results surely show that the neuroprotective effect of Delta(9)-tetrahydrocannabinol are via a CB1 receptor and temperature-dependent mechanisms whereas the neuroprotective effects of cannabidiol are independent of CB1 blockade and of hypothermia.
Repeated treatment with cannabidiol but not Delta9-tetrahydrocannabinol has a neuroprotective effect without the development of tolerance.
- Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Nanakuma 8-19-1, Fukuoka City, Fukuoka 814-0180, Japan.
Both Delta(9)-tetrahydrocannabinol (Delta(9)-THC) and cannabidiol are known to have a neuroprotective effect against cerebral ischemia. We examined whether repeated treatment with both drugs led to tolerance of their neuroprotective effects in mice subjected to 4h-middle cerebral artery (MCA) occlusion. The neuroprotective effect of Delta(9)-THC but not cannabidiol was inhibited by SR141716, cannabinoid CB(1) receptor antagonist. Fourteen-day repeated treatment with Delta(9)-THC, but not cannabidiol, led to tolerance of the neuroprotective and hypothermic effects. In addition, repeated treatment with Delta(9)-THC reversed the increase in cerebral blood flow (CBF), while cannabidiol did not reverse that effect. Repeated treatment with Delta(9)-THC caused CB(1) receptor desensitization and down-regulation in MCA occluded mice. On the contrary, cannabidiol did not influence these effects. Moreover, the neuroprotective effect and an increase in CBF induced by repeated treatment with cannabidiol were in part inhibited by WAY100135, serotonin 5-HT(1A) receptor antagonist. Cannabidiol exhibited stronger antioxidative power than Delta(9)-THC in an in vitro study using the 1,1-diphenyl-2-picryhydrazyl (DPPH) radical. Thus, cannabidiol is a potent antioxidant agent without developing tolerance to its neuroprotective effect, acting through a CB(1) receptor-independent mechanism. It is to be hoped that cannabidiol will have a palliative action and open new therapeutic possibilities for treating cerebrovascular disorders.
Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury.
- Cardiology Department, Hadassah Hebrew University Medical Center, Jerusalem, Israel. email@example.com
Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia.
Palmitoyl Serine: An Endogenous Neuroprotective Endocannabinoid-Like Entity After Traumatic Brain Injury.
- Institute for Drug Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, 91120, Israel.
The endocannabinoid (eCB) system helps recovery following traumatic brain injury (TBI). Treatment with 2-arachidonoylglycerol (2-AG), a cerebral eCB ligand, was found to ameliorate the secondary damage. Interestingly, the fatty acid amino acid amide (FAAA) N-arachidonoyl-L-serine (AraS) exerts similar eCB dependent neuroprotective. The present study aimed to investigate the effects of the FAAA palmitoyl-serine (PalmS) following TBI. We utilized the TBI model in mice to examine the therapeutic potential of PalmS, injected 1 h following closed head injury (CHI). We followed the functional recovery of the injured mice for 28 days post-CHI, and evaluated cognitive and motor function, lesion volume, cytokines levels, molecular signaling, and infarct volume at different time points after CHI. PalmS treatment led to a significant improvement of the neurobehavioral outcome of the treated mice, compared with vehicle. This effect was attenuated in the presence of eCBR antagonists and in CB2-/- mice, compared to controls. Unexpectedly, treatment with PalmS did not affect edema and lesion volume, TNFα and IL1β levels, anti-apoptotic mechanisms, nor did it exert improvement in cognitive and motor function. Finally, co-administration of PalmS, AraS and 2-AG, did not enhance the effect of the individual drugs. We suggest that the neuroprotective action of PalmS is mediated by indirect activation of the eCB receptors following TBI. One such mechanism may involve receptor palmitoylation which has been reported to result in structural stabilization of the receptors and to an increase in their activity. Further research is required in order to establish this assumption.
Endocannabinoid degradation inhibition improves neurobehavioral function, blood-brain barrier integrity, and neuroinflammation following mild traumatic brain injury.
- Department of Physiology, Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center , New Orleans, Louisiana.
Traumatic brain injury (TBI) is an increasingly frequent and poorly understood condition lacking effective therapeutic strategies. Inflammation and oxidative stress (OS) are critical components of injury, and targeted interventions to reduce their contribution to injury should improve neurobehavioral recovery and outcomes. Recent evidence reveals potential protective, yet short-lived, effects of the endocannabinoids (ECs), 2-arachidonoyl glycerol (2-AG) and N-arachidonoyl-ethanolamine (AEA), on neuroinflammatory and OS processes after TBI. The aim of this study was to determine whether EC degradation inhibition after TBI would improve neurobehavioral recovery by reducing inflammatory and oxidative damage. Adult male Sprague-Dawley rats underwent a 5-mm left lateral craniotomy, and TBI was induced by lateral fluid percussion. TBI produced apnea (17±5 sec) and a delayed righting reflex (479±21 sec). Thirty minutes post-TBI, rats were randomized to receive intraperitoneal injections of vehicle (alcohol, emulphor, and saline; 1:1:18) or a selective inhibitor of 2-AG (JZL184, 16 mg/kg) or AEA (URB597, 0.3 mg/kg) degradation. At 24 h post-TBI, animals showed significant neurological and -behavioral impairment as well as disruption of blood-brain barrier (BBB) integrity. Improved neurological and -behavioral function was observed in JZL184-treated animals. BBB integrity was protected in both JZL184- and URB597-treated animals. No significant differences in ipsilateral cortex messenger RNA expression of interleukin (IL)-1β, IL-6, chemokine (C-C motif) ligand 2, tumor necrosis factor alpha, cyclooxygenase 2 (COX2), or nicotinamide adenine dinucleotide phosphate oxidase (NOX2) and protein expression of COX2 or NOX2 were observed across experimental groups. Astrocyte and microglia activation was significantly increased post-TBI, and treatment with JZL184 or URB597 blocked activation of both cell types. These findings suggest that EC degradation inhibition post-TBI exerts neuroprotective effects. Whether repeated dosing would achieve greater protection remains to be examined.