Acute Treatment with the M-Channel (Kv7, KCNQ) Opener Retigabine Reduces the Long-Term Effects of Repetitive Blast Traumatic Brain Injuries.

We investigated whether pharmacological increase of "M-type" (KCNQ, Kv7) K + channel currents by the M-channel opener, retigabine (RTG), acutely after repetitive traumatic brain injuries (rTBIs), prevents or reduces their long-term detrimental effects. rTBIs were studied using a blast shock air wave mouse model. Animals were monitored by video and electroencephalogram (EEG) records for nine months after the last injury to assess the occurrence of post-traumatic seizures (PTS), post-traumatic epilepsy (PTE), sleep-wake cycle architecture alterations, and the power of the EEG signals. We evaluated the development of long-term changes in the brain associated with various neurodegenerative diseases in mice by examining transactive response DNA-binding protein 43 (TDP-43) expression and nerve fiber damage ~ 2 years after the rTBIs. We observed acute RTG treatment to reduce the duration of PTS and impair the development of PTE. Acute RTG treatment also prevented post-injury hypersomnia, nerve fiber damage, and cortical TDP-43 accumulation and translocation from the nucleus to the cytoplasm. Mice that developed PTE displayed impaired rapid eye movement (REM) sleep, and there were significant correlations between seizure duration and time spent in the different stages of the sleep-wake cycle. We observed acute RTG treatment to impair injury-induced reduction of age-related increase in gamma frequency power of the EGG, which has been suggested to be necessary for a healthy aged brain. The data show that RTG, administered acutely post-TBI, is a promising, novel therapeutic option to blunt/prevent several long-term effects of rTBIs. Furthermore, our results show a direct relationship between sleep architecture and PTE.

Analysis of leukocytes in medication-overuse headache, chronic migraine, and episodic migraine.

OBJECTIVE: To evaluate the number of immune cells in the peripheral blood of medication-overuse headache (MOH), chronic migraine (CM), and migraine without aura (MWA) patients, as well as from controls. BACKGROUND: Migraine has been linked to immunologic disturbances, but the role of the immune system in chronic forms of headache that evolve from migraine has not been studied. Psychiatric co-morbidity has been related to both headache chronification and immunologic alterations. METHODS: This cross-sectional study comprised 68 subjects divided in 4 groups: MOH, CM, MWA, control. Subjects were gender-matched, had no physical co-morbidity, and were taking only acetaminophen. Clinical and psychological data were recorded in a standardized protocol. Samples of peripheral blood for hematological analysis were obtained in the morning during the ictal (MOH, CM, and MWA groups) and interictal periods (MWA group), as well from control group. RESULTS: A higher lymphocyte count was measured in MOH patients relative to the MWA patients (mean ± standard deviation: 2448.7/mm3 ± 775.8 vs. 1859.7/mm3 ± 564.7; P = .027). The numbers of blood lymphocytes for CM and control subjects were 2086.1/mm3 ± 540.5 and 1961.7/mm3 ± 385.6, respectively. Multiple linear regression analysis demonstrated that only MOH and MWA groups remained associated with lymphocyte count (B = 540.7; CI 95%: 55.2-1026.1; P = .03; R2 = 19.2%). Analysis for linearity of variables in the spectrum control/MWA/CM/MOH resulted positive for body mass index (from 23.5 ± 3.25 in controls to 26.5 ± 4.49 in MOH patients; P = .034), scores on Beck Depression Inventory (from 3.29 ± 3.05 to 14.65 ± 11.21; P < 0.001) and Hamilton Anxiety Scale (from 4.29 ± 3.93 to 23.24 ± 11.01; P < 0.001), hemoglobin (from 13.7 ± 0.79 to 14.6 ± 1.31; P = .022), and lymphocyte count (from 1961.7 ± 385.6 to 2448.7 ± 775.8; P = .01), but negative for CD8+ T lymphocytes (from 34.0 ± 8.82 to 30.0 ± 6.64; P = .046). CONCLUSIONS: A higher lymphocyte count in the MOH group relative to the MWA group may indicate a chronic inflammatory state. Several clinical and laboratorial characteristics have a range along a spectrum extending from healthy subjects to patients suffering from chronic forms of migraine.

Effects of Chlorella vulgaris extract on cytokines production in Listeria monocytogenes infected mice.

In this study, we have investigated the effects of the unicellular-green-algae Chlorella vulgaris on the production of INF-gamma, IL-2, IL-4 and IL-10 in normal and Listeria monocytogenes infected mice. Our results demonstrated that in normal/non infected mice, CVE administration produced no effects in the levels of all cytokines studied. However, Listeria monocytogenes infection enhanced the production of INF-gamma and IL-2 at 48 and 72 h after the bacteria inoculation. Interestingly, the treatment with five consecutive doses of 50 mg/Kg/day of Chlorella vulgaris given previously to infection, led to further increases in INF-gamma and IL-2 levels at 48 and 72 h in relation to the presence of infection alone. No changes in IL-4 and IL-10 production were observed in Listeria monocytogenes and CVE treated/infected mice. These results are in accordance with the literature, which shows that CVE is a biological response modifier that enhances resistance to Listeria monocytogenes through augmentation of IL-2 and IFN-gamma.