Molecular determinants of behavioral changes induced by neonatal ketamine and dexmedetomidine application.

Ketamine (KET), an anesthetic, analgesic, and a sedative N-methyl-D-aspartate (NMDA) receptor antagonist agent, exposure during neonatal period may lead to learning impairment, behavioral abnormalities, and cognitive decline in the later years of life. In recent studies, it has been reported that sedative-acting α2 agonist dexmedetomidine (DEX), which is commonly used in clinical practice with KET, has neuroprotective effects and prevents the undesirable effects of anesthesia. To elucidate the underlying mechanisms of these actions, we investigated the interaction between NMDA receptors α2 adrenoceptor and adulthood behaviors in neonatally KET and/or DEX administrated mice. Balb/c male mice were administrated with saline, KET (75 mg/kg), DEX (10 µg/kg), or KET + DEX (75 mg/kg + 10 µg/kg) on postnatal day 7. During adulthood (8-10 weeks old) mice were subjected to elevated plus maze, open field, and Morris water maze tests. After behavioral tests, hippocampus samples were extracted for mRNA expression studies of NMDAR subunits (GluN1, GluN2A, and GluN2B) and α2 adrenoceptor subunits (α2A, α2B, and α2C) by real-time PCR. Ketamine increased horizontal and vertical locomotor activity (p < 0.01) and impaired spatial learning-memory (p < 0.05). DEX increased anxiety-like behavior (p < 0.01), but did not affect spatial learning-memory and locomotor activity. KET + DEX impaired spatial learning-memory (p < 0.01), increased horizontal locomotor activity (p < 0.01), and anxiety-like behavior (p < 0.05). Our study implies that DEX cannot prevent the adverse effects of KET, on spatial learning-memory, and locomotor activity. In addition to this, it can be thought that during brain development, there is an interaction between NMDAR and α2 adrenoceptor systems.

Three Dimensional Brain Parameters of Multiple Sclerosis (MS) Patients.

BACKGROUND & OBJECTIVES: MS is not only a demyelinating disease of central nervous system, but it also affects cortical and deep gray matter (GM). Furthermore, it causes axonal damage in the brain and spinal cord through inflammation and axonal degeneration. It is mostly seen between the ages of 20 and 40 and prevalence of the disease is higher among females than males. In the present study, we measured different parameters in the brains of patients with multiple sclerosis (MS) and healthy controls in both genders to determine the amount of brain atrophy quantitatively in MS patients. METHODS: We used T2-weighted MRI scans of 40 MS patients (25 females + 15 males) with clinically definite relapsing-remitting multiple sclerosis that was determined according to Poser criteria in multiple parts of the brain, and we compared these data with those of sex-matched healthy controls in the same numbers. RESULTS: Wideness of the lateral and third ventricles and the volumes of cerebral sulci in MS patients were significantly increased compared to both male and female controls. Brain width, corpus callosum area and the total brain/cerebellum + brain stem volumes of MS patients were decreased considerably. INTERPRETATION & CONCLUSIONS: The present measurements indicated that MS caused parenchymal destruction in the cortex, axonal degeneration and myelin loss in the white matter of the brain. Consequently, the current observations correlate well with worsening disability in MS patients.