Elsevier

Neuroscience Letters

Volume 259, Issue 1, 4 January 1999, Pages 21-24
Neuroscience Letters

Nicotinamide reduces infarction up to two hours after the onset of permanent focal cerebral ischemia in Wistar rats

https://doi.org/10.1016/S0304-3940(98)00881-7Get rights and content

Abstract

Ischemia depletes ATP and initiates cascades leading to irreversible tissue injury. Nicotinamide is a precursor of nicotinamide adenine dinucleotide (NAD+) which increases neuronal ATP concentration and protects against malonate-induced neurotoxicity, trauma and nitric oxide toxicity. We therefore examined whether nicotinamide could protect against stroke, using a model of permanent middle cerebral artery occlusion (MCA) occlusion in Wistar rats. Nicotinamide reduced neuronal infarction in a dose-specific manner. Furthermore, nicotinamide (500 mg/kg) reduced infarcts when administered up to 2 h after the onset of permanent MCA occlusion. The mechanism of action underlying the neuroprotection observed with nicotinamide remains to be clarified. These results are potentially important since nicotinamide is already used clinically, though not in the treatment of stroke.

Section snippets

Acknowledgements

The authors thank Dr. Adelbert Ames III and Dr. Eng H. Lo for constructive comments on the manuscript. K.I.M. is an American Heart Association Minority Scientist Development Awardee; C.S.O. is supported by NIH grant #NS01732, and M.F.B. is supported by NIH grants #NS32365 and #NS31579.

References (20)

There are more references available in the full text version of this article.

Cited by (107)

  • Pharmacokinetics of the SABRE agent 4,6-d <inf>2</inf> -nicotinamide and also nicotinamide in rats following oral and intravenous administration

    2019, European Journal of Pharmaceutical Sciences
    Citation Excerpt :

    The pharmacokinetics of NA are known to be dependent on dose, species, sex and route of administration. Safe doses in rats have previously been characterized: 750 mg/kg for subcutaneous injection and 1000 mg/kg for IP injection (Ayouba et al., 1999) Furthermore, intravenous (IV) doses of 750 mg/kg in rat models of stroke (Sakakibara et al., 2000) have been used. An in vitro cytotoxicity study demonstrated that it is possible to create a biocompatible SABRE bolus of d2-NA and that deuteration of NA does not increase the toxicity compared to the NA (Manoharan et al., 2018).

  • Nicotinamide mononucleotide inhibits post-ischemic NAD<sup>+</sup> degradation and dramatically ameliorates brain damage following global cerebral ischemia

    2016, Neurobiology of Disease
    Citation Excerpt :

    However, since PAR is consumed by poly-ADP-ribose glycohydrolase (PARG) (Davidovic et al., 2001), the above statement is valid under the assumption that there is no effect of NMN on PAR degradation by PARG. Administration of Nam also protects against excitotoxic and ischemic cell death (Ayoub et al., 1999; Yang et al., 2002a, Liu et al., 2009). It was reported that Nam exerts a number of pharmacological effects including prevention of ATP depletion (Yang et al., 2002b), inhibition of PARP1 (Klaidman et al., 1996; Yang et al., 2002b, Liu et al., 2009), lipid peroxidation (Liu et al., 2009; Klaidman et al., 2001), anti-inflammatory activity (Ungerstedt et al., 2003), and prevention of apoptosis (Klaidman et al., 1996, 2001).

View all citing articles on Scopus
View full text