Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

Lapinlampi, Niina; Andrade, Pedro; Paananen, Tomi; Hämäläinen, Elina; Ndode-Ekane, Xavier Ekolle; Puhakka, Noora; Pitkänen, Asla

doi:10.1111/epi.16632

Cited by 33 publications

(42 citation statements)

References 46 publications

(120 reference statements)

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“…Our hemorrhage-potentiating procedure did not worsen the trauma-induced learning deficits in the MWM and the MAAV tests. In line with prior literature, CCI induced deficits in visuospatial navigation in the MWM [ 43 , 44 , 45 ]. Similarly, both TBI and HTBI groups exhibited deficits in the retention of contextual learning in the MAAV test.…”

Section: Discussionsupporting

confidence: 90%

Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits

Jalloul

Hajjar

Asdikian

et al. 2021

IJMS

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Post-traumatic epilepsy (PTE) and neurocognitive deficits are devastating sequelae of head injuries that are common in adolescents. Investigating desperately needed treatments is hindered by the difficulties in inducing PTE in rodents and the lack of established immature rat models of pediatric PTE. Hemorrhage is a significant risk factor for PTE, but compared to humans, rats are less prone to bleeding because of their rapid blood coagulation system. In this study, we promoted bleeding in the controlled cortical impact (CCI) closed-head injury model with a 20 min pre-impact 600 IU/kg intraperitoneal heparin injection in postnatal day 35 (P35) periadolescent rats, given the preponderance of such injuries in this age group. Temporo-parietal CCI was performed post-heparin (HTBI group) or post-saline (TBI group). Controls were subjected to sham procedures following heparin or saline administration. Continuous long-term EEG monitoring was performed for 3 months post-CCI. Sensorimotor testing, the Morris water maze, and a modified active avoidance test were conducted between P80 and P100. Glial fibrillary acidic protein (GFAP) levels and neuronal damage were also assessed. Compared to TBI rats, HTBI rats had persistently higher EEG spiking and increased hippocampal GFAP levels (p < 0.05). No sensorimotor deficits were detected in any group. Compared to controls, both HTBI and TBI groups had a long-term hippocampal neuronal loss (p < 0.05), as well as contextual and visuospatial learning deficits (p < 0.05). The hippocampal astrogliosis and EEG spiking detected in all rats subjected to our hemorrhage-promoting procedure suggest the emergence of hyperexcitable networks and pave the way to a periadolescent PTE rat model.

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Section: Discussionsupporting

confidence: 90%

Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits

Jalloul

Hajjar

Asdikian

et al. 2021

IJMS

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“…16 Previous studies reported that severe traumatic brain injury induced by lateral fluid-percussion injury to rats caused seizures and SE. 17,18 Co implanted in the motor cortex caused focal seizures. [19][20][21] Co binds to oxygen-binding molecules and causes functional hypoxia, triggers neuronal death, and increases expression of vascular endothelial growth factor.…”

Section: Discussionmentioning

confidence: 99%

“…The cortical tissue damage caused by trauma, hemorrhage, hypoxia, and infection often leads to acute seizures and SE 16 . Previous studies reported that severe traumatic brain injury induced by lateral fluid‐percussion injury to rats caused seizures and SE 17,18 . Co implanted in the motor cortex caused focal seizures 19‐21 .…”

Section: Discussionmentioning

confidence: 99%

Neocortical injury–induced status epilepticus

2020

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Objective: To characterize neocortical onset status epilepticus (SE) in the C57BL/6J mouse. Methods: We induced SE by administering homocysteine 16-18 hours after cobalt (Co) implantation. SE was monitored by video and electroencephalography (EEG). We evaluated brain structure with magnetic resonance imaging (MRI). Neurodegeneration was evaluated 72 hours after SE using Fluoro-Jade C staining. Results: Cobalt triggered seizures in a dose-dependent manner (median effective dose, ED 50 = 0.78 mg) and the latency to peak seizure frequency shortened with increased dose. Animals developed SE after homocysteine administration. SE began with early intermittent focal seizures, consisting of frontal onset rhythmic spikewave discharges manifested as focal dystonia with clonus. These focal seizures then evolved into generalized continuous convulsive activity. Behavioral manifestations of SE included tonic stiffening, bilateral limb clonus, and bilateral tonic-clonic movements, which were accompanied by generalized rhythmic spike-wave discharges on EEG. After prolonged seizures, animals became comatose with intermittent bilateral myoclonic seizures or jerks. During this period, EEG showed seizures interspersed with generalized periodic discharges on a suppressed background. MRI obtained when animals were in a coma revealed edema, midline shift in frontal lobe around the Co implantation site, and ventricular effacement. Fluoro-Jade C staining revealed neurodegeneration in the cortex, amygdala, and thalamus. Significance: We have developed a mouse model of severe, refractory cortical-onset SE, consisting of convulsions merging into a coma, EEG patterns of cortical seizures, and injury, with evidence of widespread neocortical edema and damage. This model replicates many features of acute seizures and SE resulting from traumatic brain injury, subarachnoid, and lobar hemorrhage.

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“…Impact force, post‐impact apnea time, post‐impact seizure‐like behavior, and body weight were monitored. Occurrence of epileptic seizures was monitored during the sixth post‐injury month by continuous video‐EEG recorded 24 hours/day and 7 days/week as described previously 23–25 . All experiments were approved by the Provincial Government of Southern Finland Animal Ethics Committee and performed in accordance with the guidelines of the European Community Council Directives 2010/63/EU.…”

Section: Methodsmentioning

confidence: 99%

Acute thalamic damage as a prognostic biomarker for post‐traumatic epileptogenesis

et al. 2021

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Objective To identify magnetic resonance imaging (MRI) biomarkers for post‐traumatic epilepsy. Methods The EPITARGET (Targets and biomarkers for antiepileptogenesis, epitarget.eu) animal cohort completing T2 relaxation and diffusion tensor MRI follow‐up and 1‐month‐long video‐electroencephalography monitoring included 98 male Sprague‐Dawley rats with traumatic brain injury and 18 controls. T2 imaging was performed on day (D) 2, D7, and D21 and diffusion tensor imaging (DTI) on D7 and D21 using a 7‐Tesla Bruker PharmaScan MRI scanner. The mean and standard deviation (SD) of the T2 relaxation rate, multiple diffusivity measures, and diffusion anisotropy at each time‐point within the ventroposterolateral and ventroposteromedial thalamus were used as predictor variables in multi‐variable logistic regression models to distinguish rats with and without epilepsy. Results Twenty‐nine percent (28/98) of the rats with traumatic brain injury (TBI) developed epilepsy. The best‐performing logistic regression model utilized the D2 and D7 T2 relaxation time as well as the D7 diffusion tensor data. The model distinguished rats with and without epilepsy (Bonferroni‐corrected p‐value < .001) with a cross‐validated concordance statistic of 0.74 (95% confidence interval [CI] 0.60–0.84). In a cross‐validated classification test, the model exhibited 54% sensitivity and 91% specificity, enriching the epilepsy rate within the study population from the expected 29% to 71%. A model using the D2 T2 data only resulted in a 73% enriched epilepsy rate (regression p‐value .007, cross‐validated concordance 0.70, 95% CI 0.56–0.80, sensitivity 29%, specificity 96%). Significance An MRI parameter set reporting on acute and subacute neuropathologic changes common to experimental and human TBI presents a diagnostic biomarker for post‐traumatic epileptogenesis. Significant enrichment of the study population was achieved even when using a single time‐point measurement, producing an expected epilepsy rate of 73%.

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Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 33 publications

References 46 publications

Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits

Potentiating Hemorrhage in a Periadolescent Rat Model of Closed-Head Traumatic Brain Injury Worsens Hyperexcitability but Not Behavioral Deficits

Neocortical injury–induced status epilepticus

Acute thalamic damage as a prognostic biomarker for post‐traumatic epileptogenesis

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