David Panikashvili's research while affiliated with Hebrew University of Jerusalem and other places

Publications (10)

Article
Endocannabinoids are involved in neuroprotection through numerous biochemical pathways. We have shown that the endocannabinoid 2-arachidonoyl glycerol (2-AG) is released in mouse brain after closed head injury (CHI), and treatment with exogenous 2-AG exerts neuroprotection via the central cannabinoid receptor CB1. This process involves inhibition o...
Article
Full-text available
We reported earlier that closed head injury (CHI) in mice causes a sharp elevation of brain 2-arachidonoylglycerol (2-AG) levels, and that exogenous 2-AG reduces brain edema, infarct volume and hippocampal death and improved clinical recovery after CHI. The beneficial effect of 2-AG was attenuated by SR141716A, a CB1 cannabinoid receptor antagonist...
Article
Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries. DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)p...
Article
Closed head injury often has a devastating outcome, partly because the insult, like other injuries to the central nervous system (CNS), triggers self-destructive processes. During studies of the response to other CNS insults, it was unexpectedly discovered that the immune system, if well controlled, provides protection against self-destructive acti...
Article
Reactive oxygen species (ROS) were shown to play a role in altering blood-brain barrier (BBB) permeability and formation of brain edema induced by trauma and/or ischemia. 2-arachidonoyl glycerol (2-AG), a novel, potent vasodilatory and cytoprotective endocannabinoid has been implicated to act as an antioxidative agent. This study examines: 1) the p...
Article
Mounting in vitro and in vivo data suggest that the endocannabinoids anandamide and 2-arachidonoyl glycerol, as well as some plant and synthetic cannabinoids, have neuroprotective effects following brain injury. Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission and reduce the production of tumour necrosis factor-alpha and re...
Article
Full-text available
Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage. Protective mechanisms to attenuate damage are also set in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery and in the brain, but its physiological roles have been only partially clarified. Her...

Citations

... Levels were significantly elevated after brain injury and administration of synthetic 2-AG reduced brain edema and improved infarct volume and hippocampal death. 2-AG benefit was further evidenced by a dose dependent attenuation using SR-131761A, a CB1 receptor antagonist [58]. This neuroprotective mechanism is attributed to decreased excitotoxicity secondary to CBs NMDA receptor blockade properties. ...
... This aspect is noteworthy considering that AEA plays an antiinflammatory role in activated microglia(Correa et al., 2010;Malek, Popiolek-Barczyk, Mika, Przewlocka, & Starowicz, 2015;Pflüger-Müller et al., 2020;Sedeighzadeh, Galehdari, Tabandeh, Shamsara, & Roohbakhsh, 2021). The most relevant finding was the effect of CSE in counteracting the LPS-induced downregulation of metabolic enzymes, possibly contributing to CSE in maintaining high levels of the endocannabinoids 2-AG and AEA, whose neuroprotective role is known(Eljaschewitsch et al., 2006;Panikashvili et al., 2001;Papageorgis et al., 2011). Convincing findings have shown that activation of endocannabinoid signaling can repress microglial activation and ameliorate neurodegeneration in several neurological diseases(Tanaka et al., 2020).Interestingly, CBD was devoid of effect on the expression of the enzyme responsible for endocannabinoids metabolism in LPS- ...
... In addition to our findings on the anti-inflammatory actions of exogenous OLDA in endotoxemic and septic mice, we found that acute inflammation induced by endotoxemia modulates levels of endocannabinoids, endovanilloids, and other lipid mediators in the brain and systemic circulation. Along with reports of similar findings in the context of traumatic brain injury [101,102] or brain inflammation [103], our data suggest that the endovanilloid system and closely related endocannabinoid system may be dynamically regulated during sepsis and acute injuries to balance the early systemic inflammatory response. We speculate that systemic inflammation induces an anti-inflammatory reflex via the endogenous production of OLDA and NADA in the brain, which in turn acts on CNS TRPV1 neurons to upregulate the systemic production of IL-10, and limit downstream "bystander" organ injury. ...
... Their presence in neurological disorders suggests that CD4 + T cells are involved in neuroinflammation. Recent studies have shown that activation of calcium activated neutral protease (calpain) and CD4 + T cells are linked with the pathology of MS, PD, traumatic brain injury (TBI), spinal cord injury (SCI), and optic nerve crush injury, while calpain inhibition attenuates inflammatory T cells and promotes the recovery process Hauben and Schwartz 2003;Kipnis et al. 2003;Moalem et al. 1999;Samantaray et al. 2015). Contrary to this, the inflammatory CD4 + T cell population present in ischemia-reperfusion injury and MPTP (1methyl-4-phenyl-1,2,3,6-tetrahydropyridine) treated mice are harmful to neurons (Brochard et al. 2009;Haque et al. 2020;Hurn et al. 2007;Samantaray et al. 2015). ...
... The absorption spectra of flavins are around 450-520 nm and when activated, causes oxidation of several substances and the generation of hydrogen peroxide (García and Silva, 1997;Hockberger et al., 1999). Porphyrins are also targets of blue light and have been particularly studied in the context of photodynamic therapy (Dolmans et al., 2003;McCarron et al., 2003), but porphyrins also exist in the mitochondrial inner membrane and therefore are potentially affected by blue light (Gorgidze et al., 1998;Wataha et al., 2004). ...
... At an early stage of cerebral ischemia / reperfusion, this cascade happens in glial cells and neurons, triggering a massive inflammatory response in the brain, resulting in serious damage such as rupture of the blood-brain barrier and cerebral edoema, which is the main cause of stroke-related mortality 44 . CB1 receptor activation triggers several protective signals that involving in the phosphorylation of mitogen-activated protein kinase (MAPK) and the nuclear factor-kappa B (NF-κB) 45 . These intracellular pathways might increase neuronal survival. ...
... This lipid mediator is derived from arachidonic acid (AA) metabolism via the activation of the cyclooxygenase (COX) pathway. In the CNS, at least two COX isoforms, the constitutive (COX1) and inducible (COX2) isoforms, are expressed in neuronal and glial cells responsible for the production of the PGE 2 [15][16][17]. Both astrocytes and microglia are considered to be major sources of PGE 2 and other prostanoids within the CNS after injury or neurological disorders [17][18][19]. ...
... Treatment with nonselective cannabinoids, including endocannabinoids and synthetic molecules, has been shown to reduce proinflammatory markers in rodent models of neuroinflammation and dampen the pro-inflammatory behavior of microglia (Ehrhart et al., 2005;Eljaschewitsch et al., 2006;Fernández-López et al., 2006;Komorowska-Müller and Schmöle, 2020;Panikashvili et al., 2006;Tanaka et al., 2020). Microglia express both CB 1 and CB 2 receptors, and cross-talk can occur at the signaling level when both receptors are targeted simultaneously (Callén et al., 2012;Navarro et al., 2018a;Stella, 2010;. ...