Ketamine attenuates hypocapnia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion

• Published in: Neuroscience letters Vol. 354; no. 1; pp. 26 - 29
• Main Authors: Miyamoto, Etsuko, Nakao, Shinichi, Tomimoto, Hidekazu, Wakita, Hideaki, Yamada, Makiko, Masuzawa, Munehiro, Takahira, Kazuyo, Sakamoto, Sachiyo, Shingu, Koh
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 02.01.2004; Elsevier
• Subjects: Animals; Biological and medical sciences; Caudoputamen; Cerebral hypoperfusion; Cerebrovascular Circulation; Chronic Disease; Dementia, Vascular - drug therapy; Dementia, Vascular - etiology; Dementia, Vascular - pathology; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Hypocapnia; Hypocapnia - complications; Hypocapnia - drug therapy; Hypocapnia - pathology; Ketamine; Ketamine - pharmacology; Male; N-Methyl- d-aspartate receptor; Neostriatum - blood supply; Neostriatum - drug effects; Neostriatum - pathology; Neuronal damage; Neurons - pathology; Rats; Rats, Wistar; Respiration, Artificial - adverse effects; Vertebrates: nervous system and sense organs; White matter lesion; Neuronal damage; Ketamine; Hypocapnia; Caudoputamen; Cerebral hypoperfusion; N-Methyl- d-aspartate receptor; White matter lesion; Animal model; Central nervous system; Carbon dioxide; Glutamate receptor; White matter; Encephalon; Chronic; N-Methyl-D-aspartate receptor; Lesion; NMDA receptor
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2003.09.058

We previously demonstrated that the caudoputamen was exclusively further damaged by hypocapnia in a rat with chronic cerebral hypoperfusion which is characterized by white matter lesions (WML) and a well-established model for patients with cerebrovascular diseases and/or dementia, and suggest that this process may be the cause of long lasting postoperative delirium or brain dysfunction in such patients. In the present study, we investigated whether ketamine, a non-competitive N-methyl- d-aspartate receptor antagonist, could attenuate the neuronal damage in the caudoputamen. Ketamine, at doses of 10 and 20 mg/kg, which was given intraperitoneally before hypocapnia induction, attenuated the aggravation of WML score, neuronal damage, and astroglial proliferation in the rat caudoputamen. These results suggest that ketamine may be beneficial for preventing postoperative brain dysfunction, especially in patients with cerebrovascular diseases and/or dementia induced by hypocapnia, which is likely to occur in the mechanical ventilation used during surgery.