Radiologic evidence that hypothalamic gliosis is improved after bariatric surgery in obese women with type 2 diabetes.

BACKGROUND/OBJECTIVES: Hypothalamic neurons play a major role in the control of body mass. Obese subjects present radiologic signs of gliosis in the hypothalamus, which may reflect the damage or loss of neurons involved in whole-body energy homeostasis. It is currently unknown if hypothalamic gliosis (1) differs between obese nondiabetic (ND) and obese diabetic subjects (T2D) or (2) is modified by extensive body mass reduction via Roux-n-Y gastric bypass (RYGB). SUBJECTS/METHODS: Fifty-five subjects (all female) including lean controls (CT; n = 13), ND (n = 28), and T2D (n = 14) completed at least one study visit. Subjects underwent anthropometrics and a multi-echo MRI sequence to measure mean bilateral T2 relaxation time in the mediobasal hypothalamus (MBH) and two reference regions (amygdala and putamen). The obese groups underwent RYGB and were re-evaluated 9 months later. Analyses were by linear mixed models. RESULTS: Analyses of T2 relaxation time at baseline showed a group by region interaction only in the MBH (P < 0.0001). T2D had longer T2 relaxation times compared to either CT or ND groups. To examine the effects of RYGB on hypothalamic gliosis a three-way (group by region by time) mixed effects model adjusted for age was executed. Group by region (P < 0.0001) and region by time (P = 0.0005) interactions were significant. There was a reduction in MBH relaxation time by RYGB, and, although the T2D group still had higher T2 relaxation time overall compared to the ND group, the T2D group had significantly lower T2 relaxation time after surgery and the ND group showed a trend. The degree of reduction in MBH T2 relaxation time by RYGB was unrelated to clinical outcomes. CONCLUSION: T2 relaxation times, a marker of hypothalamic gliosis, are higher in obese women with T2D and are reduced by RYGB-induced weight loss.

Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen-level dependent response to glucose ingestion.

OBJECTIVE: In adults, hypothalamic gliosis has been documented using quantitative T2 neuroimaging, whereas functional magnetic resonance imaging (fMRI) has shown a defective hypothalamic response to nutrients. No studies have yet evaluated these hypothalamic abnormalities in children with obesity. METHODS: Children with obesity and lean controls underwent quantitative MRI measuring T2 relaxation time, along with continuous hypothalamic fMRI acquisition to evaluate early response to glucose ingestion. RESULTS: Children with obesity (N = 11) had longer T2 relaxation times, consistent with gliosis, in the mediobasal hypothalamus (MBH) compared to controls (N = 9; P = 0.004). Moreover, there was a highly significant group*region interaction (P = 0.002), demonstrating that signs of gliosis were specific to MBH and not to reference regions. Longer T2 relaxation times correlated with measures of higher adiposity, including visceral fat percentage (P = 0.01). Mean glucose-induced hypothalamic blood oxygen-level dependent signal change did not differ between groups (P = 0.11). However, mean left MBH T2 relaxation time negatively correlated with glucose-induced hypothalamic signal change (P < 0.05). CONCLUSION: Imaging signs of hypothalamic gliosis were present in children with obesity and positively associated with more severe adiposity. Children with the strongest evidence for gliosis showed the least activation after glucose ingestion. These initial findings suggest that the hypothalamus is both structurally and functionally affected in childhood obesity.

Acupuncture at ST36 exerts neuroprotective effects via inhibition of reactive astrogliosis in infantile rats with hydrocephalus.

BACKGROUND: Acupuncture has been associated with improved cerebral circulation, analgesia, neuromodulatory function and neurogenesis. In particular, acupuncture at ST36 has been widely used in several central nervous system (CNS) disorders, including neurodegenerative diseases. However, its effects on hydrocephalus have not been studied. Our aim was to evaluate the effects of acupuncture at ST36 on behaviour, motor development and reactive astrogliosis in infantile rats with hydrocephalus. METHODS: Hydrocephalus was induced in sixteen 7-day-old pup rats by injection of 20% kaolin into the cisterna magna. One day after hydrocephalus induction, acupuncture was applied once daily (for 30 min) for a total of 21 days in eight randomly selected animals (HAc group) while the remaining eight remained untreated (H group). An additional eight healthy animals were included as controls (C group). All animals were weighed daily and, from the fifth day after hydrocephalus induction, underwent MRI to determine the ventricular ratio (VR). Rats were also exposed to modified open-field tests every 3 days until the end of the experiment. After 21 days all the animals were euthanased and their brains removed for histology and immunohistochemistry. RESULTS: Hydrocephalic rats showed an increase in VR when compared with control rats (P<0.01). In addition, these animals exhibited delayed weight gain, which was attenuated with acupuncture treatment. Hydrocephalic animals treated with acupuncture performed better in open field tests (P<0.05), and had a reduction in reactive astrocyte cell density in the corpus callosum and external capsule, as assessed by GFAP (glial fibrillary acidic protein) immunohistochemistry (P<0.05). CONCLUSIONS: These findings indicate that acupuncture at ST36 has a neuroprotective potential mediated, in part, by inhibition of astrogliosis.