Midline (central) fluid percussion model of traumatic brain injury in pediatric and adolescent rats

Abstract

<jats:sec><jats:title>OBJECTIVE</jats:title><jats:p>Experimental traumatic brain injury (TBI) models hold significant validity to the human condition, with each model replicating a subset of clinical features and symptoms. TBI is the leading cause of mortality and morbidity in children and teenagers; thus, it is critical to develop preclinical models of these ages to test emerging treatments. Midline fluid percussion injury (FPI) might best represent mild and diffuse clinical brain injury because of the acute behavioral deficits, the late onset of behavioral morbidities, and the absence of gross histopathology. In this study, the authors sought to adapt a midline FPI to postnatal day (PND) 17 and 35 rats. The authors hypothesized that scaling the craniectomy size based on skull dimensions would result in a reproducible injury comparable to the standard midline FPI in adult rats.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>PND17 and PND35 rat skulls were measured, and trephines were scaled based on skull size. Custom trephines were made. Rats arrived on PND10 and were randomly assigned to one of 3 cohorts: PND17, PND35, and 2 months old. Rats were subjected to midline FPI, and the acute injury was characterized. The right reflex was recorded, injury-induced apnea was measured, injury-induced seizure was noted, and the brains were immediately examined for hematoma.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>The authors’ hypothesis was supported; scaling the trephines based on skull size led to a reproducible injury in the PND17 and PND35 rats that was comparable to the injury in a standard 2-month-old adult rat. The midline FPI suppressed the righting reflex in both the PND17 and PND35 rats. The injury induced apnea in PND17 rats that lasted significantly longer than that in PND35 and 2-month-old rats. The injury also induced seizures in 73% of PND17 rats compared with 9% of PND35 rats and 0% of 2-month-old rats. There was also a significant relationship between the righting reflex time and presence of seizure. Both PND17 and PND35 rats had visible hematomas with an intact dura, indicative of diffuse injury comparable to the injury observed in 2-month-old rats.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p>With these procedures, it becomes possible to generate brain-injured juvenile rats (pediatric [PND17] and adolescent [PND35]) for studies of injury-induced pathophysiology and behavioral deficits, for which rational therapeutic interventions can be implemented.</jats:p></jats:sec>

Noninvasive magnetic resonance imaging stratifies injury severity in a rodent model of male juvenile traumatic brain injury

“…Secondly, we only used the CCI model in this study which limits its translation to other juvenile models, such as FPI. However, moderate FPI at PND 17, similar to our study revealed hemorrhage, seizures, and increased apnea in relation to adolescent (PND 35) and adult rats (Rowe, Harrison, Ellis, Adelson, & Lifshitz, ). The temporal evolution of neuroimaging findings is likely to be different in the immature brain and is likely dependent upon the TBI model utilized, as has been reported in adult TBI (Obenaus et al, ).…”

Time course images of cellular injury and recovery in murine brain with high-resolution GRIN lens system

“…Traditionally, dental cement is used to attach an injury hub to the skull and then it is snapped off of the skull, en bloc, before the craniectomy is sealed 20 . However, the use of dental cement led to an unwanted extraction of the head plate (Fig.…”

Age-at-Injury Determines the Extent of Long-Term Neuropathology and Microgliosis After a Diffuse Brain Injury in Male Rats

“…A midline incision was made from between the eyes to just behind the ears with the fascia scraped from the skull. Various sizes of trephines were used based on the ratio of the size of the craniotomy to the size of the skull [3.0 mm (PND 17), 4.0 mm (PND35), 4.8 mm (2-, 4-, 6-months) ( 29 )] to remove a circular piece of the skull on the sagittal suture, half-way between bregma and lambda, with the dura remaining intact. The female Luer-Loc injury hub was cut from a needle and secured over the craniotomy site using cyanoacrylate gel followed by methyl-methacrylate.…”