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Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury
Neonatal Brain Disorders Center, Department of Neurology, University of California San Francisco, San Francisco, 94158 CA, USA
Neurovascular Research Unit, Department of Pharmacology, School of Medicine, Complutense University of Madrid, Madrid 28040, Spain
Department of Neonatology-Pediatrics, University Hospital Puerta de Hierro Majadahonda, Madrid 28222, Spain
* Author to whom correspondence should be addressed.
Received: 16 April 2013; in revised form: 14 May 2013 / Accepted: 26 June 2013 / Published: 10 July 2013
Abstract: Perinatal brain injury can be induced by a number of different damaging events occurring during or shortly after birth, including neonatal asphyxia, neonatal hypoxia-ischemia and stroke-induced focal ischemia. Typical manifestations of these conditions are the presence of glutamate excitoxicity, neuroinflammation and oxidative stress, the combination of which can potentially result in apoptotic-necrotic cell death, generation of brain lesions and long-lasting functional impairment. In spite of the high incidence of perinatal brain injury, the number of clinical interventions available for the treatment of the affected newborn babies is extremely limited. Hence, there is a dramatic need to develop new effective therapies aimed to prevent acute brain damage and enhance the endogenous mechanisms of long-term brain repair. The endocannabinoid system is an endogenous neuromodulatory system involved in the control of multiple central and peripheral functions. An early responder to neuronal injury, the endocannabinoid system has been described as an endogenous neuroprotective system that once activated can prevent glutamate excitotoxicity, intracellular calcium accumulation, activation of cell death pathways, microglia activation, neurovascular reactivity and infiltration of circulating leukocytes across the blood-brain barrier. The modulation of the endocannabinoid system has proven to be an effective neuroprotective strategy to prevent and reduce neonatal brain injury in different animal models and species. Also, the beneficial role of the endocannabinoid system on the control of the endogenous repairing responses (neurogenesis and white matter restoration) to neonatal brain injury has been described in independent studies. This review addresses the particular effects of several drugs that modulate the activity of the endocannabinoid system on the progression of different manifestations of perinatal brain injury during both the acute and chronic recovery phases using rodent and non-rodent animal models, and will provide a complete description of the known mechanisms that mediate such effects.
Keywords: cannabinoids; neonatal; hypoxia-ischemia; stroke; WIN55212-2; cannabidiol
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Fernández-López, D.; Lizasoain, I.; Moro, M.Á.; Martínez-Orgado, J. Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury. Brain Sci. 2013, 3, 1043-1059.
Fernández-López D, Lizasoain I, Moro MÁ, Martínez-Orgado J. Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury. Brain Sciences. 2013; 3(3):1043-1059.
Fernández-López, David; Lizasoain, Ignacio; Moro, Maria Á.; Martínez-Orgado, José. 2013. "Cannabinoids: Well-Suited Candidates for the Treatment of Perinatal Brain Injury." Brain Sci. 3, no. 3: 1043-1059.