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Abstract.Compelling evidence supports the notion that the majority of neurodegenerative diseases are associated with microglia-mediated neuroinflammation. Therefore, quelling of microglial activation may lead to neuronal cell survival. The present study investigated the effects of Kamebakaurin (KMBK), a kaurane diterpene isolated from Isodon japonicus HARA (Labiatae), on the production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated cytotoxicity in rat primary microglial cultures and the BV-2 cell line. KMBK significantly inhibited the LPSinduced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells. The mRNA and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxycenase-2 (COX-2) were also decreased dose-dependently. Furthermore KMBK inhibited the JNK and p38 mitogen-activated protein kinases (MAPKs) in LPS-stimulated BV-2 microglial cells. Considering the results obtained, the present study authenticated the potential benefits of KMBK as a therapeutic target in ameliorating microglia-mediated neuroinflammatory diseases.

Cognitive disorders can be associated with brain trauma, neurodegenerative disease or as a part of physiological aging. Aging in humans is generally associated with deterioration of cognitive performance and, in particular, learning and memory. Different therapeutic approaches are available to treat cognitive impairment during physiological aging and neurodegenerative or psychiatric disorders. Traditional herbal medicine and numerous plants, either directly as supplements or indirectly in the form of food, improve brain functions including memory and attention. More than a hundred herbal medicinal plants have been traditionally used for learning and memory improvement, but only a few have been tested in randomized clinical trials. Here, we will enumerate those medicinal plants that show positive effects on various cognitive functions in learning and memory clinical trials. Moreover, besides natural products that show promising effects in clinical trials, we briefly discuss medicinal plants that have promising experimental data or initial clinical data and might have potential to reach a clinical trial in the near future.

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks. We divided these rats into two groups and for the subsequent 6 weeks provided ad libitum feeding to half (AL, n=12) and a calorie-controlled diet to the other half (R, n=12). To avoid hypoglycemia, the degree of calorie restriction in the R group was isocaloric (g per kg body weight per day) compared with a sham-operated control group (C, n=12). During the 6-week diet control period, AL rats ate three times more than rats in the C or R groups, developing hyperglycemia with renal hyperplasia. R group achieved euglycemia but lost overall body weight significantly compared with the C or AL group (49 or 22%, respectively), heart weight (39 or 23%, respectively) and liver weight (50 or 46%, respectively). Autophagy levels in the heart and liver were the highest in the R group (P<0.01), which also had the lowest pAkt/Akt levels among the groups (P<0.05 in the heart; P<0.01 in the liver). In conclusion, glycemic control achieved by diet control can prevent hyperglycemia-induced renal hyperplasia in diabetes but may be deleterious even at isocaloric rate when insulin is deficient because of significant loss of heart and liver mass via increased autophagy.

Summary:Purpose: To assess self-awareness of complex partial seizures (CPSs) in unselected epilepsy patients through a thorough interview.Methods: The study comprised 134 patients at our epilepsy clinic, whose CPSs had been documented by the patient's family members. We investigated the proportion and characteristics of patients unaware of their CPSs compared to those who were, and we monitored the evolution of unawareness of CPSs during the follow-up.Results: Thirty-one (23%) patients were assigned to the unawareness group (complete, 23; incomplete, 8) and 103 (67%) patients to the awareness group. Patients in the unawareness group were older and had a later age of onset than patients in the awareness group. Interictal epileptiform discharges (IEDs) localized primarily to the temporal region and were more frequently detected in the unawareness group (94%) than the awareness group (55%). Bilateral independent IEDs were found more frequently in the unawareness group than in the awareness group (48% vs. 13%). The bilateral presence of lesions was also more frequent in the unawareness group than the awareness group (16.1% vs. 4.9%). Six (26%) of 23 patients with complete unawareness of their CPSs had experienced awareness of CPSs during the follow-up. Two of these patients even experienced the emergence of de novo aura.Conclusions: Our results indicate that a significant number of epilepsy patients are not aware of their CPSs. Unawareness of CPSs may be related to bitemporal dysfunction and a rapid and complete loss of consciousness caused by rapid spread of ictal discharges to the contralateral hemisphere in association with bilateral independent IEDs and bilateral presence of lesions.

Acute motor and sensory axonal neuropathy (AMSAN) are recently described subtypes of Guillain-Barre syndrome characterized by acute onset of distal weakness, loss of deep tendon reflexes, and sensory symptoms. A 21-yr-old male was transferred to our hospital due to respiration difficulties and progressive weakness. In laboratory findings, immunoglobulin M antibodies against hepatitis A were detected in blood and cerebrospinal fluid. The findings of motor nerve conduction studies showed markedly reduced amplitudes of compound muscle action potentials in bilateral peroneal, and posterior tibial nerves, without evidence of demyelination. Based on clinical features, laboratory findings, and electrophysiologic investigation, the patient was diagnosed the AMSAN following acute hepatitis A viral infection. The patient was treated with intravenous immunoglobulin and recovered slowly. Clinicians should consider this rare but a serious case of AMSAN following acute hepatitis A infection.

Palilalia is a relatively rare pathologic speech behavior and has been reported in various neuro-logic and psychiatric disorders. We encountered a case of palilalia, echolalia, and echopraxia-palipr-axia as ictal phenomena of left frontal lobe epilepsy. A 55-year-old, right-handed man was admitted because of frequent episodes of rapid reiteration of syllables. Video-electroencephalog-raphy monitoring revealed stereotypical episodes of palilalia accompanied by rhythmic head nodding and right-arm posturing with ictal discharges over the left frontocentral area. He also displayed echo-lalia or echopraxia-palipraxia, partially responding to an examiner's stimulus. Magnetic resonance imaging revealed encephalomalacia on the left superior frontal gyrus and ictal single photon emission computed tomography showed hyperperfu-sion just above the lesion, corresponding to the left supplementary motor area (SMA), and sub-cortical nuclei. This result suggests that the neuro-anatomic substrate involved in the generation of these behaviors as ictal phenomena might exist in the SMA of the left frontal lobe. Palilalia is an unsolicited reiteration of utterances recognized as a kind of motor perseveration involving the speech mechanism, frequently occurring with stereotypic prosody, accelerated rate, elevated pitch, or decreasing volume (palilalia aphone), whereas echolalia is defined as involuntary repetition of others' utterances (Duffy, 1995; Dietl et al., 2003; Christman et al., 2004). Although rarely reported, repetitive speech behaviors such as palilalia and echolalia have occurred as ictal or postictal manifestations in seizure disorders. However, the neuroanatomic correlates of those speech behaviors as ictal phenomena have not been determined. We present a case with ictal palilalia, echolalia, and echopraxia-palipraxia arising from the left frontal lobe, which was successfully documented by video-elec-troencephalography (EEG) monitoring and neuroimaging modalities. Case A 55-year-old, right-handed man was admitted to the neurology department complaining of frequent episodes of rapid repetition of meaningless syllables. Medical history was unremarkable except for chronic alcohol addiction , and he had head trauma with scalp laceration in a drunken state 6 years ago. He did not lose consciousness or show any neurologic disturbance, such as confusion or aphasia, at that time. The patient had experienced an episode of generalized tonic-clonic seizure 7 months prior to admission, but he refused medical examination at that time and continued drinking. Four months before admission , he began to have stereotypical bouts of repetition of syllables or words, three to four times daily. A diagnosis of conversion disorder and alcohol withdrawal syndrome was made at that time by his family physician; however, the spells became more frequent and had been occurring more than 10 times daily at the time of admission. During the interictal period, the patient was fully awake, and bedside neurologic examination did not show any significant n...

β-Cell function was significantly improved in patients with non-newly diagnosed and suboptimally controlled type 2 diabetes after achieving and maintaining optimal glycaemic control with long-term CSII therapy alone.