A5062355341- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Cerebrospinal fluid and hydrocephalus
- Traumatic Brain Injury and Neurovascular Disturbances
- Transcranial Magnetic Stimulation Studies
- Ion channel regulation and function
- Traumatic Brain Injury Research
- Fetal and Pediatric Neurological Disorders
- Genetics and Neurodevelopmental Disorders
- Tuberous Sclerosis Complex Research
- Pharmacological Effects and Toxicity Studies
- Neurological disorders and treatments
- Autism Spectrum Disorder Research
- Neuroscience of respiration and sleep
- Neuroscience and Neural Engineering
- Nerve injury and regeneration
- Congenital heart defects research
- Intraoperative Neuromonitoring and Anesthetic Effects
- Sleep and Wakefulness Research
- Mast cells and histamine
- Intracerebral and Subarachnoid Hemorrhage Research
- Neurogenesis and neuroplasticity mechanisms
- Sodium Intake and Health
- Amino Acid Enzymes and Metabolism
- Anesthesia and Neurotoxicity Research
Boston Children's Hospital
2014-2024
Harvard University
2013-2024
Imaging Center
2020
Drexel University
2018
Boston Children's Museum
2014
GLT-1 (EAAT2; slc1a2) is the major glutamate transporter in brain, and predominantly expressed astrocytes, but at lower levels also excitatory terminals. We generated a conditional knock-out mouse to uncover cell-type-specific functional roles of GLT-1. Inactivation gene was achieved either neurons or astrocytes by expression synapsin-Cre inducible human GFAP-CreERT2. Elimination from resulted loss ∼80% protein uptake activity that could be solubilized reconstituted liposomes. This...
Excessive extracellular glutamate after traumatic brain injury (TBI) contributes to excitotoxic cell death and likely post-traumatic epilepsy. Glutamate transport is the only known mechanism of clearance, transporter 1 (GLT-1) major mammalian brain. We tested, by immunoblot, in rat lateral fluid percussion TBI model whether GLT-1 expression depressed cortex TBI, restored treatment with ceftriaxone, a well-tolerated β-lactam antibiotic previously shown enhance noninjured animals. then tested...
Autism spectrum disorder (ASD) is a clinically and biologically heterogeneous condition characterized by social, repetitive, sensory behavioral abnormalities. No treatments are approved for the core diagnostic symptoms of ASD. To enable earliest stages therapeutic discovery development ASD, robust reproducible phenotypes biological markers essential to establish in preclinical animal models. The goal this study was identify electroencephalographic (EEG) that replicable between independent...
Many neuropsychiatric symptoms that follow traumatic brain injury (TBI), including mood disorders, sleep disturbance, chronic pain, and posttraumatic epilepsy (PTE) are attributable to compromised cortical inhibition. However, the temporal trajectory of inhibition loss its underlying mechanisms not known. Using paired-pulse transcranial magnetic stimulation (ppTMS) immunohistochemistry, we tracked functional cellular changes inhibitory network elements after fluid-percussion (FPI) in rats....
Traumatic brain injury (TBI) results in a decrease glutamate transporter-1 (GLT-1) expression, the major mechanism for removal from synapses. Coupled with an increase release dead and dying neurons, this causes extracellular glutamate. The ensuing excitotoxicity disproportionately damages vulnerable GABAergic parvalbumin-positive inhibitory interneurons, resulting progressively worsening cortical excitatory:inhibitory imbalance due to loss of tone, as evidenced by chronic post-traumatic...
Abstract Chronic symptoms indicating excess cortical excitability follow mild traumatic brain injury, particularly repetitive injury (rmTBI). Yet mechanisms underlying post-traumatic excitation/inhibition (E/I) ratio abnormalities may differ between the early and late phases. We therefore measured seizure threshold gamma-aminobutyric acid (GABA) glutamate (Glu) concentrations, 1 6 weeks after rmTBI in mice. also analyzed structure of parvalbumin-positive interneurons (PVIs), their...
Traumatic brain injury (TBI) is one of the leading causes neurological disability and death in USA across all age groups, ethnicities, incomes. In addition to short-term morbidity mortality, TBI leads epilepsy severe neurocognitive symptoms, both which are referenced post-traumatic hippocampal dysfunction, although mechanisms such dysfunction incompletely understood. Here, we study temporal profile transcription three select immediate early gene (IEG) markers neuronal hyperactivation,...
Heparin binding epidermal growth factor-like factor (HB-EGF) is an angiogenic mediating radial migration of the developing forebrain, while vascular endothelial (VEGF) known to influence rostral migratory stream in rodents. Cell defects have been identified animal models hydrocephalus; however, relationship between HB-EGF and hydrocephalus unclear. We show that mice overexpressing human with β-galactosidase reporter exhibit elevated VEGF, localization outside subventricular zone (SVZ),...
Traumatic brain injury is a leading cause of acquired epilepsy. Initially described in 1989, lateral fluid percussion (LFPI) has since become the most extensively used and well-characterized rodent traumatic post-traumatic epilepsy model. Universal findings, particularly seizures that reliably develop after an initial latent period, are evident across studies from multiple laboratories. However, LFPI procedure two-stage process, requiring surgical attachment skull cannula then reanesthesia...
Abstract Traumatic brain injury (TBI) increases cerebral reactive oxygen species production, which leads to continuing secondary neuronal after the initial insult. Cortical parvalbumin-positive interneurons (PVIs; neurons responsible for maintaining cortical inhibitory tone) are particularly vulnerable oxidative stress and thus disproportionately affected by TBI. Systemic N-acetylcysteine (NAC) treatment may restore glutathione equilibrium, preventing post-traumatic PVI loss. We therefore...
Cardiovascular diseases (CVD) are increasing at an alarming rate in South Asia. High blood pressure is a modifiable risk factor for CVD. In this study, we evaluated the control of and prevalence cardiovascular factors patients with hypertension.A cross-sectional study was conducted 50 primary health care centres throughout Pakistan. Individuals documented history hypertension, receiving pharmacological therapy, were enrolled their pressure.The recommended therapeutic hypertension (systolic...
While a noninvasive flow determination would be desirable in the diagnosis of cerebrospinal fluid shunt malfunction, existing studies have not yet defined role for thermal detection.To evaluate revised test protocol using micropumper designed to transiently enhance during testing determine whether detection is associated with progression revision surgery.Eighty-two unique tests were performed 71 shunts. The primary outcome, need within 7 d testing, was compared results micropumper-augmented...
Dravet syndrome (DS) is a monogenic, often refractory, epilepsy resultant from SCN1A haploinsufficiency in humans. A novel therapeutic target DS that can be engaged isolation or as adjunctive therapy highly desirable. Here, we demonstrate reduced expression of the rodent glutamate transporter type 1 (GLT-1) mouse model, and wild strains where Scn1a most likely to cause epilepsy, indicating GLT-1 depression may play role seizures. As upregulated by common safe FDA-approved medications, this...
Abstract Objective Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder caused by autosomal‐dominant pathogenic variants in either the TSC1 or TSC2 gene, and it characterized hamartomas multiple organs, such as skin, kidney, lung, brain. These changes can result epilepsy, learning disabilities, behavioral complications, among others. The mechanistic link between TSC target of rapamycin (mTOR) pathway well established, thus mTOR inhibitors potentially be used to treat clinical...
Abstract BACKGROUND Thermal flow evaluation (TFE) is a non-invasive method to assess ventriculoperitoneal shunt function. Flow detected by TFE negative predictor of the need for revision surgery. Further optimization testing protocols, in multiple centers, and integration with clinical imaging impressions prompted current study. OBJECTIVE To compare diagnostic accuracy 2 micropumper (TFE+MP) or without (TFE-only), neuro-imaging patients emergently presenting symptoms concerning malfunction....
Excitotoxicity is a common hallmark of epilepsy and other neurological diseases associated with elevated extracellular glutamate levels. Thus, here, we studied the protective effects (R)-AS-1, positive allosteric modulator (PAM) uptake in models.
Abstract Automated anesthesia systems that continuously monitor cortical excitability (CE) changes to govern drug infusion rates, are desirable. Paired‐pulse transcranial magnetic stimulation (ppTMS), with electromyography (EMG), provides noninvasive CE measures. We tested whether, and what temporal resolution, ppTMS‐EMG detects dose‐dependent in rats anesthetized continuous intravenous propofol. Motor‐evoked potentials (MEPs) were recorded every 20 seconds as either propofol bolus or change...