Biology subjects

Baskin, B.

Publications and source records attributed to Baskin, B..

4 recordsLinked to original sources

bioRxiv2026

Individualized and stereotypical seizure semiology in a porcine model of post-traumatic epilepsy.

Large-animal models of traumatic brain injury may yield translatable data on epileptogenesis, given their similarities in anatomy, brain size, and immune systems to humans. Adult male and female swine received bilateral cortical impact (N=16) or sham surgery (N=6) and were screened for convulsions via video-EEG for up to one year. Post-traumatic epilepsy (PTE) was defined as 2 seizures after 1-week post-injury. Nine out of sixteen pigs (56%) receiving bilateral cortical impact developed PTE, with an average 4.6 months ({+/-}3.4,SD) latent period. Seizures (N = 199) began focally, sometimes with motor onset including automatisms, before becoming generalized, with tonic-clonic or tonic convulsions. We defined a library differentiating peri-ictal behaviors (N = 31) from rhythmic/odd behaviors typical in healthy pigs (N = 12). Seizures had an average of 7.3 behaviors per seizure (max 26) lasting an average of 1.8 minutes (max 7.9). For seizures comprised of multiple convulsive episodes, the first convulsion had a greater number of peri-ictal behaviors than subsequent convulsions (P < 0.001). The array of peri-ictal behaviors displayed was pig-specific, with many behaviors consistently observed across seizures. The seizure frequency detected was 0.38/day. This large-brain model of PTE exhibits a variable period of epileptogenesis, a substantial rate of PTE, and an expansive repertoire of ictal behaviors. This first description of semiology in this species will serve as a guide for other porcine epilepsy models. Biofidelic models of PTE are expected to increase our understanding of the pathophysiology, enabling the identification and testing of therapeutics that translate into human patients. HighlightsO_LIThe average time from bilateral cortical impact to post-traumatic epilepsy in swine is 6 months, and is highly variable, ranging from 2 to 47 weeks post-TBI. C_LIO_LISwine with post-traumatic epilepsy display an array of specific behaviors around convulsions, distinct from pigs without post-traumatic epilepsy. C_LIO_LIThough the duration of convulsion was typically a few seconds, the entire seizure, with the associated peri-ictal behaviors, lasts up to 7.9 minutes. C_LIO_LIThe complexity of behaviors around convulsions tended to increase from early traumatic seizures to post-traumatic seizures. C_LIO_LIPeri-ictal behaviors observed around convulsions in an individual were often displayed prior to the first convulsion. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=115 SRC="FIGDIR/small/708000v2_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@9523aborg.highwire.dtl.DTLVardef@158cfa6org.highwire.dtl.DTLVardef@1a8b499org.highwire.dtl.DTLVardef@e8c86f_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Acute temporal, regional, and cell-type specific NKCC1 disruption following severe TBI in the developing gyrencephalic brain.

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in infants and toddlers, with limited treatment options and persistent neurological sequelae. We developed a multi-pathoanatomic lesion multi-insult (MuLMI) severe TBI model in piglets that replicates age-dependent damage patterns to the cortical ribbon observed in human patients with less injury in postnatal day (PND) 7 "infant" piglets and more extensive tissue damage in PND30 "toddler" piglets. Given that neuronal chloride homeostasis influences excitability, seizure susceptibility, and edema, we examined the developmental and injury-induced regulation of key cation-chloride cotransporters and modulators: NKCC1 (sodium-potassium-2-chloride cotransporter), KCC2 (potassium-chloride cotransporter), and the regulatory kinase SPAK, which are biomarkers of neuronal chloride concentrations. This study is the first to define the spatiotemporal expression and phosphorylation profiles of these proteins in the developing piglet brain. We found a perinatal shift in the ratio of KCC2:NKCC1 across the brain, driven primarily by protein abundance, rather than transcriptional levels. We hypothesized that toddler piglets would exhibit an increase in cortical NKCC1 and SPAK causing hyperexcitability and perhaps explaining their more severe, unilateral cortical damage. Severe TBI induced a transcriptional increase in Slc12a2 and Stk39, and a decrease in Slc12a5 in toddler piglets, but not infant piglets. We further found that infant piglets, not toddler piglets, upregulated SPAK and Tyrosine Receptor Kinase B (TRKB) protein in cortex after TBI, with minimal changes in NKCC1 and KCC2. However, phosphorylated NKCC1 (pNKCC1) was significantly upregulated in surviving cortical neurons after TBI in infant piglets and was unchanged in toddlers, despite more severe injury. These findings suggest that cortical neuronal NKCC1 activation may play a role in post-traumatic excitability or resilience in the immature brain and identify NKCC1 and/or SPAK as a potential therapeutic target. In human tissue, the KCC2:NKCC1 ratio also increased postnatally, and TBI caused region and cell-type specific dysregulation of pNKCC1. Our results establish piglets as a valuable model for investigating age-specific mechanisms of pediatric TBI and for testing targeted interventions, particularly for infant populations where seizure control remains a major clinical challenge.

neuroscience↗

bioRxiv2024

Anxiety and risk-taking behavior maps onto opioid and alcohol polysubstance consumption patterns in male and female mice

Polysubstance use is prevalent in the population but remains understudied in preclinical models. Alcohol and opioid polysubstance use is associated with negative outcomes, worse treatment prognosis, and higher overdose risk; but underlying mechanisms are still being uncovered. Examining factors that motivate use of one substance over another in different contexts in preclinical models will better our understanding of polysubstance use and improve translational value. Here we assessed baseline anxiety-like and locomotive behavior and then measured voluntary consumption of multiple doses of alcohol and fentanyl in group housed male and female mice using our novel Socially Integrated Polysubstance (SIP) system. Fifty-six male (n=32) and female (n=24) adult mice were housed in groups of 4 for one week with continuous access to food, water, two doses of ethanol (5% and 10%) and two doses of fentanyl (5 ug/ml and 20 ug/ml). Our analyses revealed sex differences across multiple domains - female mice consumed more liquid in the dark cycle, had higher activity, a higher preference for both ethanol and fentanyl over water, and their fentanyl preference increased over the seven days. Furthermore, both male and female mice displayed polysubstance consumption patterns, with female mice displaying more prolonged polysubstance use across days in the SIP chambers. We then used machine-learning techniques to reveal underlying relationships between baseline behavioral phenotypes and subsequent polysubstance consumption patterns, where anxiety- and risk-taking-like behavioral phenotypes mapped onto discrete patterns of polysubstance use, preference, and escalation. By simulating more translationally relevant substance use and improving our understanding of the motivations for different patterns of consumption, this study contributes to the developing preclinical literature on polysubstance use with the goal of facilitating better treatment outcomes and novel therapeutic strategies.

neuroscience↗

bioRxiv2022

The Dynorphin/Kappa Opioid Receptor mediates adverse immunological and behavioral outcomes induced by repetitive blast trauma in male mice

BackgroundAdverse pathophysiological and behavioral outcomes related to mild traumatic brain injury (mTBI), posttraumatic stress disorder (PTSD), and chronic pain are common following blast exposure and contribute to decreased quality of life, but underlying mechanisms and prophylactic/treatment options remain limited. The dynorphin/kappa opioid receptor (KOR) system helps regulate behavioral and inflammatory responses to stress and injury; however, it has yet to be investigated as a potential mechanism in either humans or animals exposed to blast. We hypothesized that blast-induced KOR activation mediates adverse outcomes related to inflammation and affective behavioral response. MethodsC57Bl/6 adult male mice were singly or repeatedly exposed to either sham (anesthesia only) or blast delivered by a pneumatic shock tube. The selective KOR antagonist norBNI or vehicle (saline) was administered 72 hours prior to repetitive blast or sham exposure. Serum and brain were collected 10 minutes or 4 hours post-exposure for dynorphin A-like immunoreactivity and cytokine measurements, respectively. At one-month post-exposure, mice were tested in a series of behavioral assays related to adverse outcomes reported by humans with blast trauma. ResultsRepetitive but not single blast exposure resulted in increased brain dynorphin A-like immunoreactivity. norBNI pretreatment blocked or significantly reduced blast-induced increase in serum and brain cytokines, including IL-6, at 4 hours post exposure and aversive/anxiety-like behavioral dysfunction at one month post exposure. ConclusionsOur findings demonstrate a previously unreported role for the dynorphin/KOR system as a mediator of biochemical and behavioral dysfunction following repetitive blast exposure and highlight this system as a potential prophylactic/therapeutic treatment target.

neuroscience↗