Web Application for Quantification of Traumatic Brain Injury-Induced Cortical Lesions in Adult Mice

Ciszek, Robert; Andrade, Pedro; Tapiala, Jesse; Pitkänen, Asla; Ndode-Ekane, Xavier Ekolle

doi:10.1007/s12021-019-09444-9

Cited by 3 publications

(3 citation statements)

References 6 publications

(9 reference statements)

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“…The unfolded cortical maps were generated from coronal histological sections using software developed in-house, as described previously [ 32 , 34 , 35 ]. The unfolded maps were used to determine (a) the location of the cortical lesion in various cytoarchitectonic fields of the cortical mantle, (b) the total lesion area, (c) the lesion area within different cortical cytoarchitectonic subareas, (d) the planned vs. final AP and DV coordinates of the intracerebral electrodes, and (e) the distance of the electrode tips from the lesion edge.…”

Section: Methodsmentioning

confidence: 99%

“…The unfolded maps were used to determine (a) the location of the cortical lesion in various cytoarchitectonic fields of the cortical mantle, (b) the total lesion area, (c) the lesion area within different cortical cytoarchitectonic subareas, (d) the planned vs. final AP and DV coordinates of the intracerebral electrodes, and (e) the distance of the electrode tips from the lesion edge. The unfolded map software is openly available at (accessed 30 November 2020) [ 34 ] and the source code at (accessed 30 November 2020) [ 35 ].…”

Section: Methodsmentioning

confidence: 99%

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MRI-Guided Electrode Implantation for Chronic Intracerebral Recordings in a Rat Model of Post−Traumatic Epilepsy—Challenges and Gains

et al. 2022

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Brain atrophy induced by traumatic brain injury (TBI) progresses in parallel with epileptogenesis over time, and thus accurate placement of intracerebral electrodes to monitor seizure initiation and spread at the chronic postinjury phase is challenging. We evaluated in adult male Sprague Dawley rats whether adjusting atlas-based electrode coordinates on the basis of magnetic resonance imaging (MRI) increases electrode placement accuracy and the effect of chronic electrode implantations on TBI-induced brain atrophy. One group of rats (EEG cohort) was implanted with two intracortical (anterior and posterior) and a hippocampal electrode right after TBI to target coordinates calculated using a rat brain atlas. Another group (MRI cohort) was implanted with the same electrodes, but using T2-weighted MRI to adjust the planned atlas-based 3D coordinates of each electrode. Histological analysis revealed that the anterior cortical electrode was in the cortex in 83% (25% in targeted layer V) of the EEG cohort and 76% (31%) of the MRI cohort. The posterior cortical electrode was in the cortex in 40% of the EEG cohort and 60% of the MRI cohort. Without MRI-guided adjustment of electrode tip coordinates, 58% of the posterior cortical electrodes in the MRI cohort will be in the lesion cavity, as revealed by simulated electrode placement on histological images. The hippocampal electrode was accurately placed in 82% of the EEG cohort and 86% of the MRI cohort. Misplacement of intracortical electrodes related to their rostral shift due to TBI-induced cortical and hippocampal atrophy and caudal retraction of the brain, and was more severe ipsilaterally than contralaterally ( p < 0.001). Total lesion area in cortical subfields targeted by the electrodes (primary somatosensory cortex, visual cortex) was similar between cohorts ( p > 0.05). MRI-guided adjustment of coordinates for electrodes improved the success rate of intracortical electrode tip placement nearly to that at the acute postinjury phase (68% vs. 62%), particularly in the posterior brain, which exhibited the most severe postinjury atrophy. Overall, MRI-guided electrode implantation improved the quality and interpretation of the origin of EEG-recorded signals.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

MRI-Guided Electrode Implantation for Chronic Intracerebral Recordings in a Rat Model of Post−Traumatic Epilepsy—Challenges and Gains

et al. 2022

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“…To assess the cortical lesion area and the damage to different cytoarchitectonic cortical areas after TBI as well as the treatment effect, thionin-stained sections were digitized (40×, Hamamatsu Photonics, Hamamatsu, Japan; NanoZoomer-XR, NDP.scan 3.2). Unfolded cortical maps were then prepared from the digitized histologic sections as described in detail by [32] and by applying in-house software from https://unfoldedmap.org (accessed on 14 November 2022) adapted to the rat brain [102].…”

Section: Blood Sampling and Plasma Preparationmentioning

confidence: 99%

Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology

Kajevu,

Lipponen,

Andrade

et al. 2023

IJMS

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We tested a hypothesis that in silico-discovered compounds targeting traumatic brain injury (TBI)-induced transcriptomics dysregulations will mitigate TBI-induced molecular pathology and augment the effect of co-administered antiseizure treatment, thereby alleviating functional impairment. In silico bioinformatic analysis revealed five compounds substantially affecting TBI-induced transcriptomics regulation, including calpain inhibitor, chlorpromazine, geldanamycin, tranylcypromine, and trichostatin A (TSA). In vitro exposure of neuronal-BV2-microglial co-cultures to compounds revealed that TSA had the best overall neuroprotective, antioxidative, and anti-inflammatory effects. In vivo assessment in a rat TBI model revealed that TSA as a monotherapy (1 mg/kg/d) or in combination with the antiseizure drug levetiracetam (LEV 150 mg/kg/d) mildly mitigated the increase in plasma levels of the neurofilament subunit pNF-H and cortical lesion area. The percentage of rats with seizures during 0–72 h post-injury was reduced in the following order: TBI-vehicle 80%, TBI-TSA (1 mg/kg) 86%, TBI-LEV (54 mg/kg) 50%, TBI-LEV (150 mg/kg) 40% (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 30% (p < 0.05). Cumulative seizure duration was reduced in the following order: TBI-vehicle 727 ± 688 s, TBI-TSA 898 ± 937 s, TBI-LEV (54 mg/kg) 358 ± 715 s, TBI-LEV (150 mg/kg) 42 ± 64 (p < 0.05 vs. TBI-vehicle), and TBI-LEV (150 mg/kg) combined with TSA (1 mg/kg) 109 ± 282 s (p < 0.05). This first preclinical intervention study on post-TBI acute seizures shows that a combination therapy with the tissue recovery enhancer TSA and LEV was safe but exhibited no clear benefit over LEV monotherapy on antiseizure efficacy. A longer follow-up is needed to confirm the possible beneficial effects of LEV monotherapy and combination therapy with TSA on chronic post-TBI structural and functional outcomes, including epileptogenesis.

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Seizure Susceptibility and Sleep Disturbance as Biomarkers of Epileptogenesis after Experimental TBI

et al. 2022

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Objectives: We investigated whether seizure susceptibility increases over weeks–months after experimental traumatic brain injury (TBI), and whether seizure susceptibility in rats predicts the development of post-traumatic epilepsy (PTE) or epileptiform activity. We further investigated whether rats develop chronic sleep disturbance after TBI, and whether sleep disturbance parameters—alone or in combination with pentylenetetrazol (PTZ) test parameters—could serve as novel biomarkers for the development of post-traumatic epileptogenesis. Methods: TBI was induced in adult male Sprague-Dawley rats with lateral fluid-percussion injury. Sham-operated experimental controls underwent craniectomy without exposure to an impact force. Seizure susceptibility was tested with a PTZ test (30 mg/kg, intraperitoneally) on day (D) 30, D60, D90, and D180 after TBI (n = 28) or sham operation (n = 16) under video electroencephalogram (vEEG). In the 7th post-injury month, rats underwent continuous vEEG monitoring to detect spontaneous seizures and assess sleep disturbances. At the end of the experiments, rats were perfused for brain histology. Results: In the TBI group, the percentage of rats with PTZ-induced seizures increased over time (adjusted p < 0.05 compared with D30). Combinations of three PTZ test parameters (latency to the first epileptiform discharge (ED), number of EDs, and number of PTZ-induced seizures) survived the leave-one-out validation for differentiating rats with or without epileptiform activity, indicating an area under the receiver operating curve (AUC) of 0.743 (95% CI 0.472–0.992, p = 0.05) with a misclassification rate of 36% on D90, and an AUC of 0.752 (95% CI 0.483–0.929, p < 0.05) with a misclassification rate of 32% on D180. Sleep analysis revealed that the number of transitions to N3 or rapid eye movement (REM) sleep, along with the total number of transitions, was increased in the TBI group during the lights-on period (all p < 0.05). The sleep fragmentation index during the lights-on period was greater in the TBI rats than in sham-operated rats (p < 0.05). A combination of sleep parameters showed promise as diagnostic biomarkers of prior TBI, with an AUC of 0.792 (95% CI 0.549–0.934, p < 0.01) and a misclassification rate of 28%. Rats with epilepsy or any epileptiform activity had more transitions from N3 to the awake stage (p < 0.05), and the number of N3–awake transitions differentiated rats with or without epileptiform activity, with an AUC of 0.857 (95% CI 0.651–1.063, p < 0.01). Combining sleep parameters with PTZ parameters did not improve the biomarker performance. Significance: This is the first attempt to monitor the evolution of seizure susceptibility over months in a well-described rat model of PTE. Our data suggest that assessment of seizure susceptibility and sleep disturbance can provide diagnostic biomarkers of prior TBI and prognostic biomarkers of post-traumatic epileptogenesis.

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Web Application for Quantification of Traumatic Brain Injury-Induced Cortical Lesions in Adult Mice

Cited by 3 publications

References 6 publications

MRI-Guided Electrode Implantation for Chronic Intracerebral Recordings in a Rat Model of Post−Traumatic Epilepsy—Challenges and Gains

MRI-Guided Electrode Implantation for Chronic Intracerebral Recordings in a Rat Model of Post−Traumatic Epilepsy—Challenges and Gains

Treatment of Status Epilepticus after Traumatic Brain Injury Using an Antiseizure Drug Combined with a Tissue Recovery Enhancer Revealed by Systems Biology

Seizure Susceptibility and Sleep Disturbance as Biomarkers of Epileptogenesis after Experimental TBI

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