Reduction of the infarct size by simultaneous administration of l -histidine and diphenhydramine in ischaemic rat brains

• Published in: Resuscitation 2011-02, Vol.82 (2), p.219-221
• Main Authors: Adachi, Naoto, Liu, Keyue, Ninomiya, Kanji, Matsuoka, Eiko, Motoki, Atsuko, Irisawa, Yumi, Nishibori, Masahiro
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Brain Infarction - etiology; Brain Infarction - pathology; Brain Infarction - prevention & control; Brain ischaemia; Brain Ischemia - complications; Diphenhydramine - administration & dosage; Drug therapy; Drug Therapy, Combination; Emergency; Histamine H1 Antagonists - administration & dosage; Histidine - administration & dosage; Inflammatory response; Intensive care medicine; Male; Medical sciences; Neurones; Rats; Rats, Wistar; Reperfusion; Stroke; Transfusions. Complications. Transfusion reactions. Cell and gene therapy
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/j.resuscitation.2010.10.024

Abstract Aims While diphenhydramine is a histamine H1 receptor antagonist, the agent has been shown to inhibit histamine- N -methyltransferase, a histamine inactivating enzyme in the brain. Since an increase in the brain concentration of histamine ameliorates reperfusion injury after cerebral ischaemia, effects of postischaemic administration of diphenhydramine were evaluated in rats treated with l -histidine, a precursor of histamine. Methods The right middle cerebral artery was occluded for 2 h, and the infarct size was determined 24 h after reperfusion of cerebral blood flow. Brain oedema was evaluated by comparing the area of the right hemisphere to that of the left hemisphere. Results Focal cerebral ischaemia provoked marked damage in saline-treated control rats, and infarct volumes in the striatum and cerebral cortex were 56 (49–63) mm3 and 110 (72–148) mm3 , respectively (means and 95% confidence intervals, n = 6). Administration of l -histidine (1000 mg/kg, intraperitoneal) immediately after reperfusion did not affect the infarct size. Simultaneous administration of diphenhydramine (20 mg/kg, intraperitoneal) with l -histidine reduced the infarct size to 25% and 21% of that in the control group, respectively. The combination therapy completely reduced ischaemia-induced brain oedema. Conclusion Because histamine H1 action does not influence ischaemic brain damage, elevation of the central histamine concentration by blockade of histamine- N -methyltransferase may be a likely mechanism responsible for the alleviation.