Effect of nicotinamide on focal and generalized cortical epileptic activity

Braslavskii, V. E.; Shchavelev, V. A.; Крыжановский, Г. Н.; Nikushkin, E. V.; Germanov, S. B.

doi:10.1007/bf00830710

Cited by 5 publications

(4 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NAm is also reported to be an anticonvulsant, 32,33 anticoagulant, 34 and angiogenic 35 agent and an inhibitor of lipid peroxidation. 33 Thus, there are numerous ways in which NAm could potentially act to protect against injury due to focal cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Delayed Treatment With Nicotinamide (Vitamin B ₃ ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats

Mokudai

Ayoub

Sakakibara

et al. 2000

Stroke

130

View full text Add to dashboard Cite

Background and Purpose-We have previously shown that nicotinamide (NAm) acutely reduces brain infarction induced by permanent middle cerebral artery occlusion (MCAo) in rats. In this study, we investigate whether NAm may protect against ischemia/reperfusion injury by improving sensory and motor behavior as well as brain infarction volumes in a model of transient focal cerebral ischemia. Methods-Forty-eight male Wistar rats were used, and transient focal cerebral ischemia was induced by MCAo for 2 hours, followed by reperfusion for either 3 or 7 days. Animals were treated with either intraperitoneal saline or NAm (500 mg/kg) 2 hours after the onset of MCAo (ie, on reperfusion). Sensory and motor behavior scores and body weight were obtained daily, and brain infarction volumes were measured on euthanasia. Results-Relative to treatment with saline, treatment with NAm (500 mg/kg IP) 2 hours after the onset of transient focal cerebral ischemia in Wistar rats significantly improved sensory (38%, PϽ0.005) and motor (42%, PϽ0.05) neurological behavior and weight gain (7%, PϽ0.05) up to 7 days after MCAo. The cerebral infarct volumes were also reduced 46% (PϽ0.05) at 3 days and 35% (Pϭ0.09) at 7 days after MCAo. Conclusions-NAm is a robust neuroprotective agent against ischemia/reperfusion-induced brain injury in rats, even when administered up to 2 hours after the onset of stroke. Delayed NAm treatment improved both anatomic and functional indices of brain damage. Further studies are needed to clarify whether multiple doses of NAm will improve the extent and duration of this neuroprotective effect and to determine the mechanism(s) of action underlying the neuroprotection observed. Because NAm is already used clinically in large doses and has few side effects, these results are encouraging for the further examination of the possible use of NAm as a therapeutic neuroprotective agent in the clinical treatment of acute ischemic stroke. (Stroke. 2000;31:1679-1685.)

show abstract

Section: Discussionmentioning

confidence: 99%

“…33 Thus, there are numerous ways in which NAm could potentially act to protect against injury due to focal cerebral ischemia. Experiments are presently under way to examine which action and to what extent each action contributes to the overall neuroprotective effect of NAm against focal cerebral ischemia.…”

Section: Discussionmentioning

confidence: 99%

Delayed Treatment With Nicotinamide (Vitamin B ₃ ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats

Mokudai

Ayoub

Sakakibara

et al. 2000

Stroke

130

View full text Add to dashboard Cite

show abstract

“…[15][16][17][18] Furthermore, NAm is a reported anticonvulsant, 19 anticoagulant, 20 and angiogenic agent. 21 It has been shown to attenuate lipid peroxidation, 22 stroke-induced increase in lactate in humans, 23 and inhibit inducible nitric oxide synthase mRNA. 24 Huang and Chao 25 reported an increase in regional cerebral blood flow (rCBF) after administration of NAm.…”

Section: Discussionmentioning

confidence: 99%

Delayed Multidose Treatment with Nicotinamide Extends the Degree and Duration of Neuroprotection by Reducing Infarction and Improving Behavioral Scores up to Two Weeks Following Transient Focal Cerebral Ischemia in Wistar Rats

Maynard

Ayoub

Shen

2001

Annals of the New York Academy of Sciences

View full text Add to dashboard Cite

A single, delayed dose of nicotinamide (NAm) was shown to be protective against focal cerebral ischemia in rats, but the protection was limited to three to seven days following stroke. The investigation reported here was conducted to examine if the use of multiple doses of NAm, administered after the onset of focal cerebral ischemia, would extend the duration of neuroprotection compared with a single dose treatment regimen. Male Wistar rats were subjected to transient focal cerebral ischemia by occluding the right middle cerebral artery (MCAo) for two hours. Following MCAo, motor and sensory behavioral tests were performed daily and the cerebral infarct volumes were measured at two weeks after sacrifice. Each animal was placed into one of four groups that received either normal saline alone (Group S), one (Group A), two (Group B), or three (Group C) doses of NAm (500 mg/kg). Each animal, therefore, received three treatments over two weeks, with the first dose administered intravenously two hours after the onset of MCAo. Single and multiple doses of NAm reduced the infarction (p < 0.01) and improved (p < 0.05) the neurologic sensory and motor behavior when compared with the saline‐treated animals up to two weeks after stroke. Moreover, animals that received multiple doses of NAm recuperated full motor function not different from normal, preoperative motor behavior. Delayed treatment with NAm given as multiple doses, therefore, further enhances the extent and duration of neuroprotection by significantly reducing cerebral infarct volumes, improving neurologic behavioral scores, and confers a complete motor recovery up to two weeks from the onset of focal cerebral ischemia in Wistar rats.

show abstract

“…Vitamin B 3 , as a precursor for NAD + , prevents apoptosis in the mouse brain [26,32] and in cell culture [9], is an effective antioxidant against oxidative damage in rat brain mitochondria [16,25], inhibits inducible NO synthase mRNA in glial cells and protects against trauma and NO exposure in rat hippocampus cells [15,40], and has been reported to be an inhibitor of lipid peroxidation [4]. A recent study showed that nicotinamide reduced the infarct volume following focal cerebral ischemia [36].…”

Section: Introductionmentioning

confidence: 99%

Protective Effect of Nicotinamide on Neuronal Cells under Oxygen and Glucose Deprivation and Hypoxia/Reoxygenation

Shen

Huang

et al. 2004

J Biomed Sci

View full text Add to dashboard Cite

Nicotinamide (vitamin B₃) reduces the infarct volume following focal cerebral ischemia in rats; however, its mechanism of action has not been reported. After cerebral ischemia and/or reperfusion, reactive oxygen species (ROS) and reactive nitrogen species may be generated by inflammatory cells through several cellular pathways, which can lead to intracellular calcium influx and cell damage. Therefore, we investigated the mechanisms of action of nicotinamide in neuroprotection under conditions of hypoxia/reoxygenation. Results showed that nicotinamide significantly protected rat primary cortical cells from hypoxia by reducing lactate dehydrogenase release with 1 h of oxygen-glucose deprivation (OGD) stress. ROS production and calcium influx in neuronal cells during OGD were dose-dependently diminished by up to 10 mM nicotinamide (p < 0.01). This effect was further examined with OGD/reoxygenation (H/R). Cells were stained with the fluorescent dye 4,6-diamidino-2-phenylindole (DAPI) or antibodies against anti-microtubule-associated protein-2 and cleaved caspase-3. Apoptotic cells were studied using Western blotting of cytochrome c and cleaved caspase-3. Results showed that vitamin B₃ reduced cell injury, caspase-3 cleavage and nuclear condensation (DAPI staining) in neuronal cells under H/R. In addition, nicotinamide diminished c-fos and zif268 immediate-early gene expressions following OGD. Taken together, these results indicate that the neuroprotective effect of nicotinamide might occur through these mechanisms in this in vitro ischemia/reperfusion model.

show abstract

Effect of nicotinamide on focal and generalized cortical epileptic activity

Cited by 5 publications

References 6 publications

Delayed Treatment With Nicotinamide (Vitamin B ₃ ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats

Delayed Treatment With Nicotinamide (Vitamin B ₃ ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats

Delayed Multidose Treatment with Nicotinamide Extends the Degree and Duration of Neuroprotection by Reducing Infarction and Improving Behavioral Scores up to Two Weeks Following Transient Focal Cerebral Ischemia in Wistar Rats

Protective Effect of Nicotinamide on Neuronal Cells under Oxygen and Glucose Deprivation and Hypoxia/Reoxygenation

Contact Info

Product

Resources

About

Effect of nicotinamide on focal and generalized cortical epileptic activity

Cited by 5 publications

References 6 publications

Delayed Treatment With Nicotinamide (Vitamin B 3 ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats

Delayed Treatment With Nicotinamide (Vitamin B 3 ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats

Delayed Multidose Treatment with Nicotinamide Extends the Degree and Duration of Neuroprotection by Reducing Infarction and Improving Behavioral Scores up to Two Weeks Following Transient Focal Cerebral Ischemia in Wistar Rats

Protective Effect of Nicotinamide on Neuronal Cells under Oxygen and Glucose Deprivation and Hypoxia/Reoxygenation

Contact Info

Product

Resources

About

Delayed Treatment With Nicotinamide (Vitamin B ₃ ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats

Delayed Treatment With Nicotinamide (Vitamin B ₃ ) Improves Neurological Outcome and Reduces Infarct Volume After Transient Focal Cerebral Ischemia in Wistar Rats