Braxton Norwood

• PhD Medical Pharmacology
• Lutroo Imaging

The diagnosis and understanding of pain is challenging in clinical practice. Assessing pain relies heavily on self-reporting by patients, rendering it inherently subjective. Traditional clinical imaging methods such as computed tomography and magnetic resonance imaging can only detect anatomical abnormalities, offering limited sensitivity and speci...

Voltage-gated sodium channels (Navs) play a crucial electrical signaling role in neurons. Nav-isoforms present in peripheral sensory neurons and dorsal root ganglia of the spinal cord are critically involved in pain perception and transmission. While these isoforms, particularly Nav1.7, are implicated in neuropathic pain disorders, changes in the f...

Mesial temporal lobe epilepsy (mTLE) is a common form of epilepsy and is characterized by recurrent spontaneous seizures originating from the temporal lobe. The majority of mTLE patients develop pharmacoresistance to available anti-epileptic drugs (AEDs) while exhibiting severe pathological changes that can include hippocampal atrophy, neuronal dea...

Epilepsy diagnosis is complex, requires a team of specialists and relies on in-depth patient and family history, MRI-imaging and EEG monitoring. There is therefore an unmet clinical need for a non-invasive, molecular-based, biomarker to either predict the development of epilepsy or diagnose a patient with epilepsy who may not have had a witnessed s...

Significance Temporal lobe epilepsy is commonly drug resistant and is associated with dysregulated hippocampal gene expression. MicroRNAs are short noncoding RNAs which control protein levels by binding target mRNAs via Argonaute proteins. We sequenced Argonaute-bound microRNAs from the hippocampus of three rodent epilepsy models, identifying commo...

Mesial temporal lobe epilepsy (MTLE) is a chronic neurological disorder affecting almost 40% of adult patients with epilepsy. Hippocampal sclerosis (HS) is a common histopathological abnormality found in patients with MTLE. HS is characterised by extensive neuronal loss in different hippocampus sub-regions. In this study, we used laser microdissect...

MicroRNAs (miRNAs) are short noncoding RNAs that shape the gene expression landscape, including during the pathogenesis of temporal lobe epilepsy (TLE). In order to provide a full catalog of the miRNA changes that happen during experimental TLE, we sequenced Argonaute 2-loaded miRNAs in the hippocampus of three different animal models at regular in...

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been i...

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been i...

Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been i...

A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pat...

Synaptic downscaling is a homeostatic mechanism that allows neurons to reduce firing rates during chronically elevated network activity. Although synaptic downscaling is important in neural circuit development and epilepsy, the underlying mechanisms are poorly described. We performed small RNA profiling in picrotoxin (PTX)-treated hippocampal neuro...

In order to grasp the molecular mechanisms and pathophysiology underlying epilepsy development (epileptogenesis) and epilepsy itself, it is important to understand the gene expression changes that occur during these phases. Quantitative Real-time Polymerase Chain Reaction (qPCR) is a technique that rapidly and accurately determines gene expression...

Objective: Kainic acid (KA) is a potent glutamate analog that is used to induce neurodegeneration and model temporal lobe epilepsy (TLE) in rodents. KA reliably induces severe, prolonged seizures, that is, convulsive status epilepticus (cSE), which is typically fatal without pharmacologic intervention. Although the use of KA to model human epileps...

RATIONALE: Toll-like receptors (TLR) are innate immune receptors that are important in early host defense against pathogens. TLRs recognize pathogen- or damage-associated molecular patterns (PAMPs/DAMPs). TLR4 is expressed on the cell surface and is most well-known for recognizing lipopolysaccharide (LPS), a component present in many bacteria. TLR9...

Current anti-epileptic drugs (AEDs) act on a limited set of neuronal targets, are ineffective in a third of epilepsy patients and do not show disease-modifying properties. MicroRNAs are small noncoding RNAs that regulate levels of proteins by posttranscriptional control of mRNA stability and translation. MicroRNA-134 is involved in controlling neur...

Following prolonged perforant pathway stimulation (PPS) in rats, a seizure-free “latent period” is observed that lasts around 3 weeks. During this time, aberrant neuronal activity occurs, which has been hypothesized to contribute to the generation of an “epileptic” network. This study was designed to 1) examine the pathological network activity tha...

We report here the first complete transcriptome analysis of the dorsal (dDG) and ventral dentate gyrus (vDG) of a rat epilepsy model presenting a hippocampal lesion with a strict resemblance to classical hippocampal sclerosis (HS). We collected the dDG and vDG by laser microdissection 15 days after electrical stimulation and performed high-throughp...

Animal models of convulsive status epilepticus (SE) are essential tools for studying human SE and developing novel therapies. Although they do not exhibit the prolonged“silent period” that is characteristic of the typical mesial temporal lobe epilepsy (mTLE) patient, they have proven invaluable for investigating the pathophysiology of seizure-induc...

The human serial reaction time task (SRTT) has widely been used to study the neural basis of implicit learning. It is well documented, in both human and animal studies, that striatal dopaminergic processes play a major role in this task. However, findings on the role of the hippocampus-which is mainly associated with declarative memory-in implicit...

Minocycline, a tetracycline family antibiotic, is known to inhibit microglial activation and proinflammatory cytokine release in animal models. Experimental data show that these immune processes may play a role in epilepto- and ictogenesis. We present the case of a patient with marked reduction in seizure frequency during minocycline therapy with s...

Perforant pathway stimulation (PPS) is used to study temporal lobe epilepsy in rodents. High-frequency PPS induces acute seizures, which can lead to neuron death and spontaneous epilepsy. However, the minimum duration of PPS that induces neurodegeneration in naive rodents is unknown. Freely moving Sprague-Dawley rats received one episode of continu...

Epilepsy is a common chronic neurological disorder affecting approximately 8 out of 1000 people. Its pathophysiology, however, has remained elusive in many regards. Consequently, adequate seizure control is still lacking in about one third of patients. Cytokines are soluble mediators of cell communication that are critical in immune regulation. In...

The present study examined absolute alpha power using quantitative electroencephalogram (qEEG) in bilateral temporal and parietal cortices in novice soldiers under the influence of methylphenidate (MPH) during the preparatory aiming period in a practical pistol-shooting task. We anticipated higher bi-hemispheric cortical activation in the preparato...

Involvement of the innate immune system in the pathogenesis of epilepsies has been suggested but possible interactions between the immune system and human epilepsy remain unclear. We analyzed the interictal immuno-phenotype of leukocyte subsets and proinflammatory cytokine profiles in epileptic patients and correlated them with the epilepsy syndrom...

In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called "classic hippocampal sclerosis." No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive "endstage" pathology resulting from years of spo...

Prolonged dentate granule cell discharges produce hippocampal injury and chronic epilepsy in rats. In preparing to study this epileptogenic process in genetically altered mice, we determined whether the background strain used to generate most genetically altered mice, the C57BL/6 mouse, is vulnerable to stimulation-induced seizure-induced injury. T...