Mouse closed head injury model induced by a weight-drop device

Abstract

Traumatic brain injury represents the leading cause of death in young individuals. Various animal models have been developed to mimic human closed head injury (CHI). Widely used models induce head injury by lateral fluid percussion, a controlled cortical impact or impact acceleration. The presented model induces a CHI by a standardized weight-drop device inducing a focal blunt injury over an intact skull without pre-injury manipulations. The resulting impact triggers a profound neuroinflammatory response within the intrathecal compartment with high consistency and reproducibility, leading to neurological impairment and breakdown of the blood-brain barrier. In this protocol, we define standardized procedures for inducing CHI in mice and determine various severity grades of CHI through modulation of the weight falling height. In experienced hands, this CHI model can be carried out in as little as 30 s per animal, with additional time required for subsequent posttraumatic analysis and data collection.

Inhibition of Monoacylglycerol Lipase Prevents Chronic Traumatic Encephalopathy-like Neuropathology in a Mouse Model of Repetitive Mild Closed Head Injury

“…This NSS score is within the range of the mild injury, as described previously. 26 However, the NSS scores were significantly reduced in impacted animals treated with JZL184 ( Figure 1B), indicating that inhibition of 2-AG metabolism promotes neurologic recovery following repetitive TBI. Apparently, no positive NSS scores were detected 5 days after three impacts in both vehicle-or JZL184-treated TBI animals, suggesting that neurologic injuries are completely recovered 5 days after the impacts.…”

“…The neurological severity score (NSS), ratings from 0 (normal) to 10 (severely impaired) as described previously, 26 was assessed to determine motor and reflex function, flexion of limbs, and resistance to position changes 2 hours after each impact and 5 days after three impacts.…”

“…14,15,19,21,27 JZL184 (10 mg/kg) was injected 30 minutes after each TBI and then once a day for 4 consecutive days ( Figure 1A). The neurologic severity score (NSS), which includes 10 tasks as described previously, 26 was assessed to determine the functional status of animals after rmCHI. We found that the NSS score was increased with the increased number of impacts and displayed a cumulative effect.…”

Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury

“…Neurological severity scoring (NSS) has previously been shown to strongly correlate with the extent of TBI in a range of animal model systems 28 . We used a 10-point NSS scale that has been described previously and has been adapted for use with our model system.…”

“…A measure of neurological severity was obtained using ten tests for markers of motor and cognitive function, as previously described 28 . The tests were performed by an individual blinded to the experimental treatment and were as follows: exit a circle with a diameter of 30 cm within 3 min; ability to use all 4 limbs; initiative and ability to walk straight; startle reflex; seeking behaviour; ability to balance on a beam 7 mm wide for 10 s; cross a 30 cm beam of width 3 cm in 3 min; same test, beam narrowed to 2 cm; same test, beam narrowed to 1 cm; ability to perch on a round beam of width 5 mm.…”