87 One initial longitudinal MRS study found brain regional increases in NAA levels in individuals with BPD

and healthy subjects treated for 4 weeks with lithium,79 a finding replicated by other investigators.88-90 NAA levels were also found to be correlated with brain lithium levels in a study of elderly patients with BPD.91 Valproate was similarly found to increase hippocampal NAA levels.72 Mood stabilizers produce neuroprotective effects in animal models of disease Mood stabilizers are known Inhibitors,research,lifescience,medical to protect cultured cells from a variety of insults (for reviews see refs 6,7,92,93). In this section, we review the neuroprotective effects of lithium and valproate in a series of models of brain ischemia, neurodegeneration, and neuroinflammation (eg, cerebral ischemia, Alzheimer’s Inhibitors,research,lifescience,medical disease (AD), Huntington’s disease, amyotrophic lateral sclerosis

(ALS), HIV- associated cognitive impairments, and spinocerebellar ataxia). In a seminal study using an animal model of ischemia, Chuang and colleagues found that ischemic infarct size induced by occlusion of the left middle cerebral artery was markedly reduced by lithium buy Z-VAD-FMK treatment administered before94 or after95 Inhibitors,research,lifescience,medical the induction of ischemia; these findings have since been replicated by other investigators.96-104 Follow-up studies showed that valproate had similar protective effects on ischemia-induced brain infarction.105,106 ALS is a progressive, Inhibitors,research,lifescience,medical lethal neurodegenerative disease with no known cure. Riluzole, which prolongs the survival of patients by several months, is the only FDAapproved treatment for this disease. Interestingly, Inhibitors,research,lifescience,medical riluzole itself has been associated with neuroprotective properties.107

SOD1-G93A mice, a model for ALS, carry a high copy number of this transgene with the G93A human SOD1 mutation. Studies show that valproate108 and lithium109,110 both delay disease Histone demethylase onset and prolong lifespan in SOD1-G93A mice. Furthermore, lithium and valproate together produce an additive protective effect in SOD1-G93A mice compared with either treatment alone.110 Notably, a clinical trial found that lithium, compared with riluzole, further delays disease progression and death in individuals with ALS.109 With regards to AD, diverse studies have suggested that lithium’s neuroprotective effects may have a potential role in the therapeutics of this disease. AD is a leading cause of dementia in the aging population and the most common neurodegenerative disease without an effective treatment.