A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Mychasiuk, Richelle; Farran, Allyson; Angoa‐Pérez, Mariana; Briggs, D.W.; Kuhn, Donald M.; Esser, Michael J.

doi:10.3791/51820-v

Cited by 5 publications

(5 citation statements)

References 3 publications

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“…This weight drop method effectively reproduces a clinically relevant "concussion-like" mTBI including replication of the biomechanics reported in humans (e.g. unrestrained head, linear and rotational acceleration) and without induction of significant gross or histological brain damage, no skull fractures and minimal loss of consciousness (34,37,38). We have recently used this mTBI model to demonstrate transient acute cephalic and hindpaw allodynia that can be reinstated by stress and is a surrogate for APTH and PPTH, respectively (35,36,39).…”

Section: Introductionmentioning

confidence: 61%

“…Development of PTH is the most common symptom following a mild traumatic brain injury (mTBI). Through our previous work we have validated a closed head injury weight drop model that recapitulates the biomechanics of a mTBI in humans without induction of significant neuropathology (34,37,38). In accordance with our previous work, even a single mTBI is capable of inducing acute pain-like behaviors (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache

Rudolph,

Kopruszinski,

et al. 2023

Cephalalgia

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Background Post-traumatic headache is very common after a mild traumatic brain injury. Post-traumatic headache may persist for months to years after an injury in a substantial proportion of people. The pathophysiology underlying post-traumatic headache remains unknown but is likely distinct from other headache disorders. Identification of brain areas activated in acute and persistent phases of post-traumatic headache can provide insights into the underlying circuits mediating headache pain. We used an animal model of mild traumatic brain injury-induced post-traumatic headache and c-fos immunohistochemistry to identify brain regions with peak activity levels across the acute and persistent phases of post-traumatic headache. Methods Male and female C57BL/6 J mice were briefly anesthetized and subjected to a sham procedure or a weight drop closed-head mild traumatic brain injury . Cutaneous allodynia was assessed in the periorbital and hindpaw regions using von Frey filaments. Immunohistochemical c-fos based neural activity mapping was then performed on sections from whole brain across the development of post-traumatic headache (i.e. peak of the acute phase at 2 days post- mild traumatic brain injury), start of the persistent phase (i.e. >14 days post-mild traumatic brain injury) or after provocation with stress (bright light). Brain areas with consistent and peak levels of c-fos expression across mild traumatic brain injury induced post-traumatic headache were identified and included for further analysis. Results Following mild traumatic brain injury, periorbital and hindpaw allodynia was observed in both male and female mice. This allodynia was transient and subsided within the first 14 days post-mild traumatic brain injury and is representative of acute post-traumatic headache. After this acute post-traumatic headache phase, exposure of mild traumatic brain injury mice to a bright light stress reinstated periorbital and hindpaw allodynia for several hours – indicative of the development of persistent post-traumatic headache. Acute post-traumatic headache was coincident with an increase in neuronal c-fos labeling in the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and the nucleus accumbens. Neuronal activation returned to baseline levels by the persistent post-traumatic headache phase in the spinal nucleus of the trigeminal caudalis and primary somatosensory cortex but remained elevated in the nucleus accumbens. In the persistent post-traumatic headache phase, coincident with allodynia observed following bright light stress, we observed bright light stress-induced c-fos neural activation in the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and nucleus accumbens. Conclusion Examination of mild traumatic brain injury-induced changes in peak c-fos expression revealed brain regions with significantly increased neural activity across the acute and persistent phases of post-traumatic headache. Our findings suggest mild traumatic brain injury-induced post-traumatic headache produces neural activation along pain relevant pathways at time-points matching post-traumatic headache-like pain behaviors. These observations suggest that the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and nucleus accumbens may contribute to both the induction and maintenance of post-traumatic headache.

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Section: Introductionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache

Rudolph,

Kopruszinski,

et al. 2023

Cephalalgia

View full text Add to dashboard Cite

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“…This procedure was adapted from Mychasiuk et al, 2014 ) ( Mychasiuk et al, 2014 ). At P28 rats were placed in a pre-primed isoflurane chamber with 5% isoflurane in 100% oxygen for 45 s to induce anesthesia.…”

Section: Methodsmentioning

confidence: 99%

In utero and post-natal opioid exposure followed by mild traumatic brain injury contributes to cortical neuroinflammation, mitochondrial dysfunction, and behavioral deficits in juvenile rats

Gowen

Jing

Stauch

et al. 2023

Brain, Behavior, & Immunity - Health

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“…A modified closed‐head weight‐drop model (Mychasiuk et al, 2014) was performed as follows: 20‐PND male and female rats were lightly anaesthetised with 2% isoflurane in air until the toe pinch response had disappeared. Animals were placed in a prone position on tinfoil below the head injury device so that the skull region between coronal and lambdoid sutures was centred beneath the weight drop path.…”

Section: Methodsmentioning

confidence: 99%

“…SHAM rats received isoflurane anaesthesia only, without the trauma procedure. Loss of righting reflex was used as confirmation of injury and the righting reflex latency (time taken for animals to return to a standing position from the supine position following removal of anaesthetic) was measured and used as a marker of injury severity as it reflects the loss of consciousness (Mychasiuk et al, 2014) (Figure S1C). Animals in which loss of consciousness was less than 180 s were not considered.…”

Section: Methodsmentioning

confidence: 99%

Acute intranasal treatment with nerve growth factor limits the onset of traumatic brain injury in young rats

Manni

Leotta

Mollica

et al. 2023

British J Pharmacology

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Background and Purpose: Traumatic brain injury (TBI) comprises a primary injury directly induced by impact, which progresses into a secondary injury leading to neuroinflammation, reactive astrogliosis, and cognitive and motor damage. To date, treatment of TBI consists solely of palliative therapies that do not prevent and/or limit the outcomes of secondary damage and only stabilize the deficits. The neurotrophin, nerve growth factor (NGF), delivered to the brain parenchyma following intranasal application, could be a useful means of limiting or improving the outcomes of the secondary injury, as suggested by pre-clinical and clinical data.Experimental Approach: We evaluated the effect of acute intranasal treatment of young (20-postnatal day) rats, with NGF in a TBI model (weight drop/close head), aggravated by hypoxic complications. Immediately after the trauma, rats were intranasally treated with human recombinant NGF (50 μgÁkg À1 ), and motor behavioural test, morphometric and biochemical assays were carried out 24 h later.

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A Novel Model of Mild Traumatic Brain Injury for Juvenile Rats

Cited by 5 publications

References 3 publications

Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache

Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache

In utero and post-natal opioid exposure followed by mild traumatic brain injury contributes to cortical neuroinflammation, mitochondrial dysfunction, and behavioral deficits in juvenile rats

Acute intranasal treatment with nerve growth factor limits the onset of traumatic brain injury in young rats

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