Efficacy and Safety of Cilostazol in Mild Cognitive Impairment: A Randomized Clinical Trial.

Importance: Recent evidence indicates the efficacy of β-amyloid immunotherapy for the treatment of Alzheimer disease, highlighting the need to promote β-amyloid removal from the brain. Cilostazol, a selective type 3 phosphodiesterase inhibitor, promotes such clearance by facilitating intramural periarterial drainage.

Objective: To determine the safety and efficacy of cilostazol in mild cognitive impairment.

[A case of neuromyelitis optica spectrum disorders, with slowly progressive bulbar palsy, mimicking a motor neuron disease].

A 52-year old woman first noted dysphagia four months before admission followed by dysarthria two months later. She then developed weakness of all limbs and became unable to walk. All these symptoms, associated with tongue atrophy, slowly progressed, leading to the initial clinical impression of a motor neuron disease, although her nerve conduction study and electromyography showed no abnormalities.

[A case of limbic encephalitis associated with Sjögren's syndrome mimicking anti N-methyl D-aspartate receptor encephalitis].

A 25-year-old woman in her 37 weeks and 5 days pregnant presented with abnormal behavior and memory impairment following a high fever. Her manifestations were diagnosed as limbic encephalitis, and she delivered a baby by Cesarean section. In the operation, bilateral ovarian tumors were found and resected, though they were revealed as non-teratoma afterward.

Heat-shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase: clues to a possible strategy for treating ALS.

A dominant mutation in the gene for copper-zinc superoxide dismutase (SOD1) is the most frequent cause of the inherited form of amyotrophic lateral sclerosis. Mutant SOD1 provokes progressive degeneration of motor neurons by an unidentified acquired toxicity. Exploiting both affinity purification and mass spectrometry, we identified a novel interaction between heat-shock protein 105 (Hsp105) and mutant SOD1.

Protective effect of serofendic acid on glutamate-induced neurotoxicity in rat cultured motor neurons.

We have previously reported that a sulfur-containing neuroprotective substance named serofendic acid was purified and isolated from lipophilic extract of fetal calf serum (FCS). In the present study, we investigated the effect of serofendic acid on glutamate neurotoxicity using embryonic rat spinal cord culture. When cultures were exposed to glutamate (20 microM) with a glutamate transporter inhibitor L-trans-pyrrolidine-2,4-decarboxylate (PDC; 40 microM) for 24 h, motor neurons were injured through both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole/kainate receptors.

Stimulation of nicotinic acetylcholine receptors protects motor neurons.

The present study demonstrated that administration of nicotine prevented glutamate-induced motor neuronal death in primary cultures of the rat spinal cord. The nicotine-induced neuroprotection was inhibited by either dihydro-beta-erythroidin (DHbetaE) or alpha-bungarotoxin (alphaBT), suggesting that it is mediated through both alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs). Both alpha4beta2 and alpha7 nAChRs were identified on rat spinal motor neurons by immunohistochemical methods.

Galantamine modulates nicotinic receptor and blocks Abeta-enhanced glutamate toxicity.

Galantamine is a plant alkaloid that is used in the treatment of Alzheimer's disease. We have studied the effects of galantamine on beta-amyloid-enhanced glutamate toxicity using primary rat cultured cortical neurons. Nicotine and galantamine alone, and in combination, protected neurons against this neurotoxicity.

Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons.

Glutamate-induced excitotoxicity is implicated as playing a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), and mitochondrial dysfunction is also found in ALS patients. We investigated the relationship between glutamate excitotoxicity and mitochondrial dysfunction elicited by rotenone (a complex I inhibitor), malonate (a complex II inhibitor), or antimycin (a complex III inhibitor), in primary cultures of the embryonic rat spinal cord. Rotenone and malonate induced relatively selective toxicity against motor neurons as compared to non-motor neurons, whereas antimycin caused non-selective toxicity.

Phosphodiesterase inhibitors are neuroprotective to cultured spinal motor neurons.

We have previously reported that cyclic guanosine-3',5'-monophosphate (cGMP) protects spinal motor neurons against acute reactive oxygen species (ROS)-induced toxicity but not against chronic ROS-induced or glutamate (Glu)-induced toxicity. In this study, we investigated the effects of phosphodiesterase (PDE) inhibitors on the survival of cultured spinal motor neurons. Selective PDE5 inhibitors (dipyridamole, T-1032, and zaprinast) as well as a nonselective PDE inhibitor (aminophylline) protected motor and nonmotor neurons against both acute ROS-induced and chronic Glu-induced neurotoxicity, whereas selective inhibitors of PDE1-4 offered no protection.

Protective effect of dopamine D2 agonists in cortical neurons via the phosphatidylinositol 3 kinase cascade.

Glutamate, one of the excitatory neurotransmitters, contributes to the neuronal death associated with neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and with ischemia. In Alzheimer's disease brains, there is a decreased number of dopamine D2 receptors, which might cause neuronal dysfunction or death. In the present study, bromocriptine exerted a protective effect against glutamate-induced cytotoxicity in rat cortical neurons.

Estradiol protects dopaminergic neurons in a MPP+Parkinson's disease model.

The prevalence of Parkinson's disease is higher in males than in females. Although the reason for this gender difference is not clear, the level of female steroid hormones or their receptors may be involved in the pathogenesis. The estrogen receptor subtype expressed in the midbrain is limited to the novel beta subtype, whose role in the central nervous system has not been resolved.