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Background: N(2-propylpentanoyl) urea (VPU) is a new valproic acid (VPA) analog with higher anticonvulsant activity than its parent compound in various animal models including seizure acutely induced by pilocarpine. Objective: Investigate its effects on hippocampal amino acid neurotransmitters in spontaneous recurrent seizure (SRS) rats. Methods: Pilocarpine hydrochloride was used to induce status epilepticus (SE). Animals were visually observed for two hours/day for an episode of SRS for six weeks. Microdialysis experiment was performed to detect hippocampal amino acid neurotransmitters on those rats that developed SRS. Results: In comparison to normal rats, hippocampal glutamate, gamma-aminobutyric acid (GABA), and glycine, significantly increased in SRS rats. Occurrence of SRS in the faces of increased level of inhibitory neurotransmitters suggests the key role played by glutamate in the genesis and control of SRS. Based on the observation in pilocarpine-induced SE, the level of glutamate in SRS rats significantly decreased by a clinically effective anticonvulsant, VPA (300 and 600 mg/kg, i.p). Similar profile on hippocampal glutamate was also exhibited by VPU (50 and 100 mg/kg, i.p.). Conclusion: The possible role of VPU in controlling seizure in SRS rats and subsequently human temporal lobe epilepsy as VPA was suggested.

Bacopa monnieri (L.) Wettst. (Brahmi) is a traditional memory enhancer partly by improved cerebral blood flow. Here we sought to link improved cognitive function with better blood flow in randomised double-blinded placebo-controlled trial in an elderly cohort. Normotensive Thais, aged 55-80y having mini-mental state examination (MMSE) scores > 25, no dementia or other psycho/neurological disease, normal lipid profile, and blood biochemistry were recruited. The trial design was a 2 week run-in, 12 week intervention of test product or placebo, and 4 week washout. The intervention was an extract of B. monnieri leaves (eBM) in 40 ml of mulberry juice. The placebo contained mulberry juice and other constituents to match gustatory properties. End-points were a battery of memory functions, carotid blood velocity, post-ischemic microvascular blood flow, markers of vascular inflammation, blood pressure and the blood markers. Response latency was reduced by 14.2 ± 4.9% (p = 0.022 comparing placebo) but only in > 65s. Other memory recall parameters were either unaffected or for ‘accuracy of recall’ was already maximal preventing further improvement. No change was detected in carotid blood velocity while microvascular blood flow marginally increased (by 28.4 ± 8.3%, p = 0.07). This preliminary evidence warrant further studies on selected patients with microvascular cognitive dysfunction using more discriminating protocols.

In Alzheimer's disease, there are numerous amyloid plaques, neurofibrillary tangles, and neuronal loss in several brain areas. Oxidative stress is involved in the mechanisms of Aβ-peptide induced neurotoxicity by the generation of free radical oxidative stress that may lead to neurodegeneration. Tabernaemontana divaricata has various medical properties in Thai folklore medicine including prevent forgetfulness or improve memory. The present study aimed to investigate the effects of T. divaricata root extract (TDE) on Aβ25–35 peptides induced neuronal loss and oxidative stress in mice. Male ICR mice were administered with vehicle or TDE (250, 500, and 1000 mg/kg b.w., p.o.) for 28 consecutive days. Then, these mice were given a single intracerebroventricular (i.c.v.) injection of Aβ25–35 or phosphate buffer saline (PBS) (10 μg/mouse). The novel object recognition (NOR) test was used to determine memory disturbance. In addition, the neuronal cells in the cerebral cortex and hippocampus were measured by using crystal violet staining and lipid peroxidation was determined by measuring the formation of thiobarbituric acid reactive substances. An i.c.v. injection of Aβ25–35 peptides could significantly induce memory impairment, increase level of lipid peroxidation including the neuronal loss in CA3 of hippocampus. However, the mice pretreated with TDE could prevent the memory loss, neuronal loss and decrease lipid peroxidation. These results suggest the potential therapeutic value in dementia of TDE through its antioxidant property.

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Oxidative stress is one of the major factors that contributes to brain deterioration in the elderly. Oxidation causes molecular alterations, structural damage, and brain dysfunction, which includes cognitive impairment. Memory loss can begin in middle-aged individuals, so prevention of brain deterioration before aging is important. Several studies have reported that curcumin and γ-oryzanol exhibits anti-oxidant and anti-inflammatory properties. However, curcumin and γ-oryzanol exhibit low aqueous solubility. Thus, a solid dispersion technique was used to prepare curcumin and γ-oryzanol to enhance their solubility and stability. This study aims to evaluate the effects and mechanisms of γ-oryzanol solid dispersion (GOSD) and curcumin solid dispersion (CURSD) on learning and memory in six groups of male rats (n=5/group). Group one was the adult control consisting of 6-week old male rats, and the remaining five groups consisted of 42-week (middle-aged) male rats. The groups were labeled as the control group, the GO group (GOSD 10 mg/kg•BW), the Cur group (CURSD 50 mg/kg•BW), the GO-LCur group (GOSD 10 mg/kg•BW plus CURSD 25 mg/kg•BW), and the GO-HCur group (GOSD 10 mg/kg•BW plus CURSD 50 mg/kg•BW). Substances were administrated by oral gavage once daily for 42 consecutive days. The GO-HCur group exhibited significantly increased learning and memory performance in a Morris water maze and in reacting to a spontaneous tendency novel object test. The rats also exhibited decreased levels of lipid peroxidation, increased superoxide dismutase levels, glutathione peroxidase levels, catalase activity, and enhanced c-Fos expression both in the hippocampus and prefrontal cortex. The results indicated that GOSD 10 mg/kg plus CURSD 50 mg/kg was able to enhance learning and memory performance in the middle-aged rats.