ABSTRACT
Mild traumatic brain injury (mTBI) is a debilitating but extremely common form of brain injury that affects a substantial number of people each year. mTBI is especially common in children and adolescents. Our understanding of mTBI pathophysiology is limited, and there is currently no accepted marker for disease severity. A potential marker for disease severity may be cerebrovascular dysfunction. Recent findings have implicated cerebrovascular alteration as an important component of mTBI and suggest it contributes to the development of persistent, long-term symptoms. In this paper, we conducted two studies to investigate whether mTBI affects venous drainage patterns in the central nervous system using alterations in the size of venous sinuses as a marker of changes in drainage. Using a closed head vertical weight-drop model and a lateral impact injury model of mTBI, we imaged and quantified the size of three major draining vessels in the adolescent rat brain using 9.4T MRI. Areas and volumes were quantified in the superior sagittal sinus and left and right transverse sinuses using images acquired from T2w MRI in one study and post-gadolinium T1w MRI in another. Our results indicated that the three venous sinuses were significantly larger in mTBI rats as compared to sham rats 1-day post injury but recovered to normal size 2 weeks after. Acutely enlarged sinuses post-mTBI may indicate abnormal venous drainage, and this could be suggestive of a cerebrovascular response to trauma.
ABSTRACT
Between July of 2012 and December of 2014, 39 patients were enrolled prospectively to investigate the prevalence of glucose transporter 1 (GLUT1) deficiency in a ketogenic diet clinic. None of them had GLUT1 deficiency. All patients seen in the same clinic within the same period were reviewed retrospectively. A total of 18 of these 85 patients had a genetic diagnosis, including GLUT1 deficiency, pathogenic copy number variants, congenital disorder of glycosylation, neuronal ceroid lipofuscinosis type II, mitochondrial disorders, tuberous sclerosis, lissencephaly, and SCN1A-, SCN8A-, and STXBP1-associated epileptic encephalopathies. The prevalence of genetic diagnoses was 21% and prevalence of GLUT1 deficiency was 2.4% in our retrospective cohort study.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/complications , Carbohydrate Metabolism, Inborn Errors/genetics , Diet, Ketogenic/methods , Epilepsy/complications , Monosaccharide Transport Proteins/deficiency , Adolescent , Carbohydrate Metabolism, Inborn Errors/diet therapy , Carbohydrate Metabolism, Inborn Errors/epidemiology , Child , Child, Preschool , Cohort Studies , Epilepsy/diet therapy , Epilepsy/epidemiology , Epilepsy/genetics , Female , Humans , Male , Monosaccharide Transport Proteins/genetics , PrevalenceABSTRACT
RATIONALE: Enhancement of the endocannabinoid (EC) system may reduce anticipatory nausea (AN). OBJECTIVES: The experiments evaluated the potential of the dual fatty acid amide hydrolase (FAAH)/monoacylglycerol lipase (MAGL) inhibitor, JZL195, on its own and combined with anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) to reduce contextually elicited gaping, a measure of AN in rats. METHODS: Following four context lithium chloride (LiCl) pairings, rats were injected with vehicle (VEH) or JZL195 (10 mg kg(-1), intraperitoneally) 105 min before an injection of VEH, 2-AG (1.25 mg kg(-1)), or AEA (5.0 mg kg(-1)). Fifteen minutes later, all rats were placed in the LiCl-paired context for 5 min and in a different context for a 15-min locomotor test. Whole brains were extracted for EC analysis. The potential of the CB1 antagonist, SR141716, to reverse the suppression of AN by both JZL195 and AEA and of the CB2 antagonist, AM630, to reverse the suppression of AN by JZL195 was then evaluated. RESULTS: JZL195 suppressed gaping and elevated AEA, palmitoylethanolamine, and oleoylethanolamide. As the suppression of gaping was reversed by SR141716, but not by AM630, the effect was CB1 mediated. The suppressive effect of JZL195 on gaping, as well as elevation of AEA and 2-AG, was amplified by pretreatment with either AEA or 2-AG. On its own, AEA, but not 2-AG, also suppressed gaping-an effect that was also prevented by CB1 antagonism. CONCLUSIONS: JZL195 reduces AN primarily by acting as a FAAH inhibitor, but MAGL inhibition is also indicated.
