Intraperitoneal cannabidiol attenuates neonatal germinal matrix hemorrhage-induced neuroinflamation and perilesional apoptosis

• Published in: Neurological research (New York) Vol. 41; no. 11; pp. 980 - 990
• Main Authors: Abrantes De Lacerda Almeida, Timóteo, Santos, Marcelo Volpon, Da Silva Lopes, Luiza, Goel, Gunjan, Leonardo De Freitas, Renato, De Medeiros, Priscila, Crippa, José Alexandre, Machado, Hélio Rubens
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02-11-2019
• Subjects: Animals; Animals, Newborn; Apoptosis - drug effects; Brain - drug effects; Brain - pathology; Brain Edema - complications; Brain Edema - pathology; Cannabidiol; Cannabidiol - administration & dosage; Cannabidiol - pharmacology; Cerebral Hemorrhage - complications; Cerebral Hemorrhage - drug therapy; Cerebral Hemorrhage - pathology; Disease Models, Animal; germinal matrix hemorrhage; immunohistochemistry; inflammation; Intracranial Hemorrhages - complications; Intracranial Hemorrhages - drug therapy; Male; neuroprotection; Neuroprotective Agents - pharmacology; Rats, Wistar; Cannabidiol; germinal matrix hemorrhage; immunohistochemistry; inflammation; neuroprotection
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2019.1651487

Background. As the survival of preterm infants has increased significantly, germinal matrix hemorrhage (GMH) has become an important public health issue. Nevertheless, treatment strategies for the direct neuronal injury are still scarce. The present study aims to analyze the neuroprotective properties of cannabidiol in germinal matrix hemorrhage.
Methods. 112 Wistar rat pups (P7) were submitted to an experimental collagenase induced model of GMH. Inflammatory response and neuronal death were analyzed both at the perilesional area as at the distant ipsilateral CA1 hippocampal area. Immunohistochemistry for GFAP and caspase 3 was used. The ipsilateral free water content was assessed for stimation of cerebral edema, and neurodevelopment and neurofunctional tests were conducted.
Results. Reduction of reactive astrocytosis was observed both in the perilesional area 24 hours and 14 days after the hemorrhage lesion (p < 0.001) and in the Stratum oriens of the ipsilateral hippocampal CA1 14 days after the hemorrhage lesion (p < 0.05) in the treated groups. Similarly, there was a reduction in the number of Caspase 3-positive astrocytes in the perilesional area in the treated groups 24 hours after the hemorrhage lesion (p < 0.001). Finally, we found a significant increase in the weight of the rats treated with cannabidiol.
Conclusion. The treatment of GMH with cannabidiol significantly reduced the number of apoptotic cells and reactive astrocytes in the perilesional area and the ipsilateral hippocampus. In addition, this response was sustained 14 days after the hemorrhage. These results corroborate our hypothesis that cannabidiol is a potential neuroprotective agent in the treatment of germinal matrix hemorrhage.