Visualization of mouse barrel cortex using ex-vivo track density imaging

We describe the visualization of the barrel cortex of the primary somatosensory area (S1) of ex vivo adult mouse brain with short-tracks track density imaging (stTDI). stTDI produced much higher definition of barrel structures than conventional fractional anisotropy (FA), directionally-encoded color FA maps, spin-echo and T2-weighted imaging and gradient echo Ti/T2*-weighted imaging. 3D high angular resolution diffusion imaging (HARDI) data were acquired at 48 micron isotropic resolution for a (3 mm)3 block of cortex containing the barrel field and reconstructed using stTDI at 10 micron isotropic resolution. HARDI data were also acquired at 100 micron isotropic resolution to image the whole brain and reconstructed using stTDI at 20 micron isotropic resolution. The 10 micron resolution stTDI maps showed exceptionally clear delineation of barrel structures. Individual barrels could also be distinguished in the 20 micron stTDI maps but the septa separating the individual barrels appeared thicker compared to the 10 micron maps, indicating that the ability of stTDI to produce high quality structural delineation is dependent upon acquisition resolution. Close homology was observed between the barrel structure delineated using stTDI and reconstructed histological data from the same samples. stTDI also detects barrel deletions in the posterior medial barrel sub-field in mice with infraorbital nerve cuts. The results demonstrate that stTDI is a novel imaging technique that enables three-dimensional characterization of complex structures such as the barrels in S1 and provides an important complementary non-invasive imaging tool for studying synaptic connectivity, development and plasticity of the sensory system. (C) 2013 Elsevier Inc. All rights reserved

Posttraumatic epilepsy induced by lateral fluid-percussion brain injury in rats

Although traumatic brain injury is a major cause of symptomatic epilepsy, the mechanism by which it leads to recurrent seizures is unknown. An animal model of posttraumatic epilepsy that reliably reproduces the clinical sequelae of human traumatic brain injury is essential to identify the molecular and cellular substrates of posttraumatic epileptogenesis, and perform preclinical screening of new antiepileptogenic compounds. We studied the electrophysiologic, behavioral, and structural features of posttraumatic epilepsy induced by severe, non-penetrating lateral fluid-percussion brain injury in rats. Data from two independent experiments indicated that 43% to 50% of injured animals developed epilepsy, with a latency period between 7 weeks to 1 year. Mean seizure frequency was 0.3±0.2 seizures per day and mean seizure duration was 113±46 s. Behavioral seizure severity increased over time in the majority of animals. Secondarily-generalized seizures comprised an average of 66±37% of all seizures. Mossy fiber sprouting was increased in the ipsilateral hippocampus of animals with posttraumatic epilepsy compared with those subjected to traumatic brain injury without epilepsy. Stereologic cell counts indicated a loss of dentate hilar neurons ipsilaterally following traumatic brain injury. Our data suggest that posttraumatic epilepsy occurs with a frequency of 40% to 50% after severe non-penetrating fluid-percussion brain injury in rats, and that the lateral fluid percussion model can serve as a clinically-relevant tool for pathophysiologic and preclinical studies. © 2006 IBRO

From traumatic brain injury to posttraumatic epilepsy: What animal models tell us about the process and treatment options

A large number of animal models of traumatic brain injury (TBI) are already available for studies on mechanisms and experimental treatments of TBI. Immediate and early seizures have been described in many of these models with focal or mixed type (both gray and white matter damage) injury. Recent long-term video-electroencephalography (EEG) monitoring studies have demonstrated that TBI produced by lateral fluid-percussion injury in rats results in the development of late seizures, that is, epilepsy. These animals develop hippocampal alterations that are well described in status epilepticus–induced spontaneous seizure models and human posttraumatic epilepsy (PTE). In addition, these rats have damage ipsilaterally in the cortical injury site and thalamus. Although studies in the trauma field provide a large amount of information about the molecular and cellular alterations corresponding to the immediate and early phases of PTE, chronic studies relevant to the epileptogenesis phase are sparse. Moreover, despite the multiple preclinical pharmacologic and cell therapy trials, there is no information available describing whether these therapeutic approaches aimed at improving posttraumatic recovery would also affect the development of lowered seizure threshold and epilepsy. To make progress, there is an obvious need for information exchange between the trauma and epilepsy fields. In addition, the inclusion of epilepsy as an outcome measure in preclinical trials aiming at improving somatomotor and cognitive recovery after TBI would provide valuable information about possible new avenues for antiepileptogenic interventions and disease modification after TBI

MRI biomarkers for post-traumatic epileptogenesis

The present study tested a hypothesis that early identification of injury severity with quantitative magnetic resonance imaging (MRI) provides biomarkers for predicting increased seizure susceptibility and epileptogenesis after traumatic brain injury (TBI). TBI was induced by lateral fluid percussion injury (FPI) in adult rats. Quantitative T2, T1ρ, and diffusion were assessed with MRI at 9 days, 23 days, or 2 months post-TBI in the perilesional cortex, thalamus, and hippocampus. Seizure susceptibility was assessed at 12 months after TBI using the pentylenetetrazol seizure-susceptibility test. At 9 and 23 days post-TBI, a change in T1ρ of the perilesional cortex showed the greatest predictive value for increased seizure susceptibility at 12 months post-TBI [area under the curve (AUC), 0.929 and 0.952, respectively;

Mouse EEG spike detection based on the adapted continuous wavelet transform

Objective. Electroencephalography (EEG) is an important tool in the diagnosis of epilepsy. Interictal spikes on EEG are used to monitor the development of epilepsy and the effects of drug therapy. EEG recordings are generally long and the data voluminous. Thus developing a sensitive and reliable automated algorithm for analyzing EEG data is necessary. Approach. A new algorithm for detecting and classifying interictal spikes in mouse EEG recordings is proposed, based on the adapted continuous wavelet transform (CWT). The construction of the adapted mother wavelet is founded on a template obtained from a sample comprising the first few minutes of an EEG data set. Main Result. The algorithm was tested with EEG data from a mouse model of epilepsy and experimental results showed that the algorithm could distinguish EEG spikes from other transient waveforms with a high degree of sensitivity and specificity. Significance. Differing from existing approaches, the proposed approach combines wavelet denoising, to isolate transient signals, with adapted CWT-based template matching, to detect true interictal spikes. Using the adapted wavelet constructed from a predefined template, the adapted CWT is calculated on small EEG segments to fit dynamical changes in the EEG recording