Jessin K John, Adam M Robin, Aqueel H Pabaney, Richard A Rammo, Lonni R Schultz, Neema S Sadry, Ian Y Lee
Journal of Neurosurgery (Nov 2016)
Recent studies have demonstrated that periventricular tumor location is associated with poorer survival and that tumor location near the ventricle limits the extent of resection. This finding may relate to the perception that ventricular entry leads to further complications and thus surgeons may choose to perform less aggressive resection in these areas. However, there is little support for this view in the literature. This study seeks to determine whether ventricular entry is associated with more complications during craniotomy for brain tumor resection.
Li Zhang, Michael Chopp, Yanlu Zhang, Ye Xiong, Chao Li, Neema Sadry, Imane Rhaleb, Mei Lu, Zheng Gang Zhang
Stroke - American Heart Association (Aug 2016)
Diabetes mellitus (DM) is a common metabolic disease among the middle-aged and older population, which leads to an increase of stroke incidence and poor stroke recovery. The present study was designed to investigate the impact of DM on brain damage and on ischemic brain repair after stroke in aging animals.
Quan Jiang, Li Zhang, Guangliang Ding, Esmaeil Davoodi-Bojd, Qingjiang Li, Lian Li, Neema Sadry, Maiken Nedergaard, Michael Chopp, Zhenggang Zhang
Journal of Cerebral Blood Flow & Metabolism (Apr 2016)
The glymphatic system has recently been shown to clear brain extracellular solutes and abnormalities in glymphaticclearance system may contribute to both initiation and progression of neurological diseases. Despite that diabetes isknown as a risk factor for vascular diseases, little is known how diabetes affects the glymphatic system. The current studyis the first investigation of the effect of diabetes on the glymphatic system and the link between alteration of glymphaticclearance and cognitive impairment in Type-2 diabetes mellitus rats. MRI analysis revealed that clearance of cerebrospinalfluid contrast agent Gd-DTPA from the interstitial space was slowed by a factor of three in the hippocampus of Type-2diabetes mellitus rats compared to the non-DM rats and confirmed by florescence imaging analysis. Cognitive deficitsdetected by behavioral tests were highly and inversely correlated to the retention of Gd-DTPA contrast and fluorescenttracer in the hippocampus of Type-2 diabetes mellitus rats. Type-2 diabetes mellitus suppresses clearance of interstitialfluid in the hippocampus and hypothalamus, suggesting that an impairment of the glymphatic system contributes to Type-2 diabetes mellitus-induced cognitive deficits. Whole brain MRI provides a sensitive, non-invasive tool to quantitativelyevaluate cerebrospinal fluid and interstitial fluid exchange in Type-2 diabetes mellitus and possibly in other neurologicaldisorders, with potential clinical application.
Haifa Kassis, Amjad Shehadah, Chao Li, Yi Zhang, Yisheng Cui, Cynthia Roberts, Neema Sadry, Xianshuang Liu, Michael Chopp, Zheng Gang Zhang
Neurochemistry International (Jun 2016)
We have previously demonstrated that stroke induces nuclear shuttling of class IIa histone deacetylase 4 (HDAC4). Stroke-induced nuclear shuttling of HDAC4 is positively and significantly correlated with improved indices of neuronal remodeling in the peri-infarct cortex. In this study, using a rat model for middle cerebral artery occlusion (MCAO), we tested the effects of selective inhibition of class IIa HDACs on functional recovery and neuronal remodeling when administered 24hr after stroke. Adult male Wistar rats (n = 15–17/group) were subjected to 2 h MCAO and orally gavaged with MC1568 (a selective class IIa HDAC inhibitor), SAHA (a non-selective HDAC inhibitor), or vehicle-control for 7 days starting 24 h after MCAO. A battery of behavioral tests was performed. Lesion volume measurement and immunohistochemistry were performed 28 days after MCAO. We found that stroke increased total HDAC activity in the ipsilateral hemisphere compared to the contralateral hemisphere. Stroke-increased HDAC activity was significantly decreased by the administration of SAHA as well as by MC1568. However, SAHA significantly improved functional outcome compared to vehicle control, whereas selective class IIa inhibition with MC1568 increased mortality and lesion volume and did not improve functional outcome. In addition, MC1568 decreased microtubule associated protein 2 (MAP2, dendrites), phosphorylated neurofilament heavy chain (pNFH, axons) and myelin basic protein (MBP, myelination) immunoreactivity in the peri-infarct cortex. Quantitative RT-PCR of cortical neurons isolated by laser capture microdissection revealed that MC1568, but not SAHA, downregulated CREB and c-fos expression. Additionally, MC1568 decreased the expression of phosphorylated CREB (active) in neurons. Taken together, these findings demonstrate that selective inhibition of class IIa HDACs impairs neuronal remodeling and neurological outcome. Inactivation of CREB and c-fos by MC1568 likely contributes to this detrimental effect.
