neuropeptide-y and Brain-Injuries--Traumatic

Interventions for preventing cognitive dysfunction after traumatic brain injury (TBI) are limited. Given that adult hippocampal neurogenesis after brain injury contributes to cognitive recovery, and hippocampal neurogenesis is potentially affected by nutritional factors, the aim of this study was to examine whether fasting could promote hippocampal neurogenesis and thus ameliorate the cognitive defects after TBI.. The present study used 8- to 10-wk-old C57 BL/6 N mice weighing 23 g, half males and half females. The mice were randomly assigned to each group, with 10 to 18 mice per group. All mice were housed in an approved animal facility with a 12-h light/dark cycle. In the metabolic study (food intake, body weight, blood glucose, triacylglycerol, total cholesterol, and β-hydroxybutyric acid ), 54 mice (male:female = 1:1) were randomized to the ad libitum (AL) group (n = 18) and the intermittent fasting (IF) group (n = 36). In the neurogenesis study, 45 mice (male:female = 1:1) were randomized to AL (n  = 18), IF (n  = 9), IF + scramble (n  = 9), and the IF + neuropeptide Y (NPY)_siRNA (n  = 9) groups. In the Morris water maze test, 48 mice (male:female = 1:1) were randomized to AL (n  = 12), IF (n  = 12), IF + scramble (n  = 12), and the IF + NPY_siRNA (n  = 12) groups.. We showed that a 1-mo-long IF regimen enhanced the proliferation of neural stem cells in the subgranular zone of the hippocampus 3 d after TBI, in addition to improving the cognitive performance in the Morris water maze test. Furthermore, an increase in the hippocampal NPY expression was detected in the IF group after the injury, compared with the mice fed AL, and local knockdown of NPY in vivo attenuated the effects of IF on TBI.. These findings suggest that IF promotes hippocampal neurogenesis after TBI by a mechanism that involves enhancement of NPY expression, to alleviate cognitive dysfunction caused by injury.

Topics: Animals; Brain Injuries, Traumatic; Fasting; Female; Hippocampus; Male; Maze Learning; Mice; Mice, Inbred C57BL; Neurogenesis; Neurons; Neuropeptide Y; RNA, Small Interfering

Anxiety outcomes after traumatic brain injury (TBI) are complex, and the underlying neural mechanisms are poorly understood. Here, we developed a multi-dimensional behavioral profiling approach to investigate anxiety-like outcomes in mice that takes into account individual variability. Departing from the tradition of comparing outcomes in TBI versus sham groups, we identified a subgroup within the TBI group that is vulnerable to anxiety dysfunction, and present increased exploration of the anxiogenic zone compared to sham controls or resilient injured animals, by applying dimensionality reduction, clustering, and

Topics: Animals; Anxiety; Biomarkers; Brain Injuries, Traumatic; gamma-Aminobutyric Acid; Male; Maze Learning; Mice; Mice, Inbred C57BL; Neuropeptide Y

This study assessed neuropeptide Y (NPY) expression in the hippocampus after long-term survival following traumatic brain injury (TBI) induced by controlled cortical impact (CCI) with or without the development of posttraumatic epilepsy (PTE). We hypothesized that following long-term survival after CCI, the severity of tissue injury and the development of PTE would correlate with the degree of hippocampal neurodegeneration as reflected by NPY+ and neuronal nuclear antigen (NeuN)+ cell loss. Adult Sprague-Dawley rats of 2-3 months of age were lesioned in the right parietal cortex and monitored for seizure activity by video and/or video-EEG. Neuropeptide Y and NeuN immunoreactivities (IRs) were quantified by light microscopy and semiautomatic image analysis approaches for unbiased quantification. Severely injured animals, marked by extensive tissue loss in the ipsilateral neocortex and adjacent hippocampus, resulted in significantly lower NeuN+ hilar cell density and NPY+ cell loss in the contralateral Cornu Ammonis (CA)-3 and dentate hilus (DH). The degree of NPY+ cell loss was more severe in CCI-injured animals with PTE than those animals that did not develop PTE. Mildly injured animals demonstrated no significant change of NPY expression compared with control animals. Our findings of long-term alterations of NPY expression in the hippocampus of severely brain-injured animals can provide important insights into the cellular and molecular consequences of severe TBI and posttraumatic epileptogenesis.

Topics: Animals; Brain Injuries, Traumatic; Cerebral Cortex; Electroencephalography; Epilepsy, Post-Traumatic; Gene Expression; Hippocampus; Male; Neurons; Neuropeptide Y; Rats; Rats, Sprague-Dawley

There is growing evidence that physical activity ameliorates the course of epilepsy in animal models as well as in clinical conditions. Since traumatic brain injury is one of the strongest determinants of epileptogenesis, the present study focuses on the question whether a moderate long-term physical training can decrease susceptibility to seizures evoked following brain damage. Wistar rats received a mechanical brain injury and were subjected to daily running sessions on a treadmill for 21 days. Thereafter, seizures were induced by pilocarpine injections in trained and non-trained, control groups. During the acute period of status epilepticus, the intensity of seizures was assessed within the six-hour observation period. The trained rats showed considerable amelioration of pilocarpine-induced motor symptoms when compared with their non-trained counterparts. Histological investigations of effects of the brain injury and of physical training detected significant quantitative changes in parvalbumin-, calretinin- and NPY-immunopositive neuronal populations. Some of the injury-induced changes, especially those shoved by parvalbumin-immunopositive neurons, were abolished by the subsequent physical training procedure and could, therefore, be considered as neuronal correlates of the observed functional amelioration of the injured brain.

Topics: Animals; Brain; Brain Injuries, Traumatic; Calbindin 2; Glial Fibrillary Acidic Protein; Male; Neurons; Neuropeptide Y; Parvalbumins; Physical Conditioning, Animal; Pilocarpine; Rats; Rats, Wistar; Seizures; Status Epilepticus