[Show abstract][Hide abstract] ABSTRACT: 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 T1-, T2- and gradient echo T1/T2*-weighted imaging. 3D high angular resolution diffusion imaging (HARDI) data were acquired at 48 micron isotropic resolution for a (3mm)(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.
[Show abstract][Hide abstract] ABSTRACT: The complex pathogenesis of temporal lobe epilepsy includes neuronal and glial pathology, synaptic reorganization, and an immune response. However, the spatio-temporal pattern of structural changes in the brain that provide a substrate for seizure generation and modulate the seizure phenotype is yet to be completely elucidated. We used quantitative magnetic resonance imaging (MRI) to study structural changes triggered by status epilepticus (SE) and their association with epileptogenesis and with activation of complement component 3 (C3). SE was induced by injection of pilocarpine in CD1 mice. Quantitative diffusion-weighted imaging and T2 relaxometry was performed using a 16.4-Tesla MRI scanner at 3 h and 1, 2, 7, 14, 28, 35, and 49 days post-SE. Following longitudinal MRI examinations, spontaneous recurrent seizures and interictal spikes were quantified using continuous video-EEG monitoring. Immunohistochemical analysis of C3 expression was performed at 48 h, 7 days, and 4 months post-SE. MRI changes were dynamic, reflecting different outcomes in relation to the development of epilepsy. Apparent diffusion coefficient changes in the hippocampus at 7 days post-SE correlated with the severity of the evolving epilepsy. C3 activation was found in all stages of epileptogenesis within the areas with significant MRI changes and correlated with the severity of epileptic condition.
Brain Structure and Function 03/2013; 219(2). DOI:10.1007/s00429-013-0528-4 · 5.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 in adult rats. Quantitative T2, T1ρ, and diffusion were assessed with MRI at 9 d, 23 d, 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 d post-TBI, a change in T1ρ of the perilesional cortex showed the greatest predictive value for increased seizure susceptibility at 12 months post-TBI (AUC 0.929 and 0.952, respectively, p<0.01). At 2 months post-TBI, Dav in the thalamus was the best of the biomarkers analyzed (AUC 0.988, p<0.05). The highest predictive value of all biomarkers was achieved by combining the measurement of Dav in the perilesional cortex and the thalamus at 2 months post-TBI (AUC 1.000, p<0.01). Our results provide proof-of-concept evidence that clinically relevant MR imaging biomarkers predict increased seizure susceptibility after experimental TBI.
Journal of neurotrauma 03/2013; 30(14). DOI:10.1089/neu.2012.2815 · 3.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Posttraumatic epilepsy is a common consequence of traumatic brain injury in humans. Major predictors for the development of posttraumatic epilepsy include the severity of injury and occurrence of cortical contusions. The effect of the size or location of the cortical lesion on the risk of epileptogenesis, however, is poorly understood. Here, we investigated the extent and location of cortical damage and its association with a lowered seizure threshold and the occurrence of spontaneous seizures in rats (n=77) that had experienced moderate or severe lateral fluid-percussion brain injury (FPBI) 12 months earlier. Spontaneous seizures were detected with video-electroencephalography monitoring and a lowered seizure threshold was determined based on a pentylenetetrazol (PTZ) test. Cortical atrophy was evaluated from thionin-stained sections using the Cavalieri estimation in four different experiments in which rats developed either spontaneous recurrent seizures (i.e., epilepsy) or a lowered seizure threshold. Our data show that damage to the cortex ipsilateral to the injury was more severe and extended more caudally in epileptic animals than in those without epilepsy (p<0.05 and p<0.001 for 2 independent experiments). Further, the extent of the cortical damage correlated positively with chronically increased hyperexcitability (number of spikes in PTZ test) in animals with traumatic brain injury (r=-0.54, p<0.05; r=-0.72, p<0.01 for 2 independent experiments). Specifically, cortical lesions located at the level of the perirhinal, entorhinal, and postrhinal cortices were associated with a lowered seizure threshold and seizures. The severity of the cortical injury did not correlate with the severity of hippocampal damage. These findings indicate that, like in humans, the severity of cortical injury correlates with epileptogenesis and epilepsy in an experimental model of posttraumatic epilepsy.
Epilepsy research 06/2010; 90(1-2):47-59. DOI:10.1016/j.eplepsyres.2010.03.007 · 2.02 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to focus on recent advances in understanding of the genetic and epidemiologic risk factors, development, modeling, and prevention of epilepsy after traumatic brain injury (TBI).
Epidemiologic data suggest that the epileptogenic period after TBI in humans may last longer than previously thought. Depression was found to be an important risk factor for posttraumatic epilepsy (PTE). Once PTE has developed, it remits less often than previously reported. Moreover, patients with PTE appear to have a higher mortality rate than patients with TBI without epilepsy. In animal models it was reported that in addition to rats, also mice develop PTE. Furthermore, the immature rat brain is sensitive to TBI-induced epileptogenesis. The development of a lowered seizure threshold after TBI can be alleviated by pharmacotherapy in rats.
These observations provide small but encouraging steps towards a better understanding of the mechanisms of posttraumatic epileptogenesis, which is a key to developing a cure for this condition.
Current opinion in neurology 04/2010; 23(2):183-8. DOI:10.1097/WCO.0b013e32833749e4 · 5.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severity of traumatic brain injury (TBI) positively correlates with the risk of post-traumatic epilepsy (PTE). Studies on post-traumatic epileptogenesis would greatly benefit from markers that at acute phase would reliably predict the extent and severity of histologic brain damage caused by TBI in individual subjects. Currently in experimental models, severity of TBI is determined by the pressure of applied load that does not directly reflect the extent of inflicted brain injury, mortality within experimental population, or impairment in behavioral tests that are laborious to perform. We aimed to compare MRI markers measured at acute post-injury phase to previously used indicators of injury severity in the ability to predict the extent of histologically determined post-traumatic tissue damage. We used lateral fluid-percussion injury model in rat that is a clinically relevant model of closed head injury in humans, and results in PTE in severe cases. Rats (48 injured, 12 controls) were divided into moderate (mTBI) and severe (sTBI) groups according to impact strength. MRI data (T2, T2*, lesion volume) were acquired 3 days post-injury. Motor deficits were analysed using neuroscore (NS) and beam balance (BB) tests 2 and 3 days post-injury, respectively. Histological evaluation of lesion volume (Fluoro-Jade B) was used as the reference outcome measure, and was performed 2 weeks after TBI. From MRI parameters studied, quantitative T2 values of cortical lesion not only correlated with histologic lesion volume (P<0.001, r=0.6, N=34), as well as NS (P<0.01, r=-0.5, N=34) and BB (P<0.01, r=-0.5, N=34) results, but also successfully differentiated animals with mTBI from those with sTBI 70.6 +/- 6.2 6.2 ms vs. 75.9 +/- 2.6 ms, P<0.001). Quantitative T2 of the lesion early after TBI can serve as an indicator of the severity of post-traumatic cortical damage and neuro-motor impairment, and has a potential as a clinical marker for identification of individuals with elevated risk of PTE.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: In traumatic brain injury (TBI) the initial impact causes both immediate damage and also launches a cascade of slowly progressive secondary damage. The chronic outcome disabilities vary greatly and can occur several years later. The aim of this study was to find predictive factors for the long-term outcome using multiparametric, non-invasive magnetic resonance imaging (MRI) methodology and a clinically relevant rat model of fluid percussion induced TBI. Our results demonstrated that the multiparametric quantitative MRI (T(2), T(1rho), trace of the diffusion tensor D(av), the extent of hyperintense lesion and intracerebral hemorrhage) acquired during acute and sub acute phases 3 h, 3 days, 9 days and 23 days post-injury has potential to predict the functional and histopathological outcome 6 to 12 months later. The acute D(av) changes in the ipsilateral hippocampus correlated with the chronic spatial learning and memory impairment evaluated using the Morris water maze (p<0.05). Similarly, T(1rho), T(2) and D(av) correlated with hippocampal atrophy and with histologically quantified neurodegeneration (p<0.01). The early lesion volume and quantitative MRI changes in the perilesional region prefigured the final lesion extent (p<0.01). Furthermore, the severity of acute intracerebral hemorrhage correlated with the final cortical atrophy (p<0.05), hippocampal atrophy (p<0.01), and also with the water maze performance (p<0.01). We conclude that, assessment of early quantitative MRI changes in the hippocampus and in the perifocal area may help to predict the long-term outcome after experimental TBI.
[Show abstract][Hide abstract] ABSTRACT: To understand the dynamics of progressive brain damage after lateral fluid-percussion induced traumatic brain injury (TBI) in rat, which is the most widely used animal model of closed head TBI in humans, MRI follow-up of 11 months was performed. The evolution of tissue damage was quantified using MRI contrast parameters T(2), T(1rho), diffusion (D(av)), and tissue atrophy in the focal cortical lesion and adjacent areas: the perifocal and contralateral cortex, and the ipsilateral and contralateral hippocampus. In the primary cortical lesion area, which undergoes remarkable irreversible pathologic changes, MRI alterations start at 3 h post-injury and continue to progress for up to 6 months. In more mildly affected perifocal and hippocampal regions, the robust alterations in T(2), T(1rho), and D(av) at 3 h to 3 d post-injury normalize within the next 9-23 d, and thereafter, progressively increase for several weeks. The severity of damage in the perifocal and hippocampal areas 23 d post-injury appeared independent of the focal lesion volume. Magnetic resonance spectroscopy (MRS) performed at 5 and 10 months post-injury detected metabolic alterations in the ipsilateral hippocampus, suggesting ongoing neurodegeneration and inflammation. Our data show that TBI induced by lateral fluid-percussion injury triggers long-lasting alterations with region-dependent temporal profiles. Importantly, the temporal pattern in MRI parameters during the first 23 d post-injury can indicate the regions that will develop secondary damage. This information is valuable for targeting and timing interventions in studies aiming at alleviating or reversing the molecular and/or cellular cascades causing the delayed injury.
[Show abstract][Hide abstract] ABSTRACT: We tested a hypothesis that manganese enhanced magnetic resonance imaging (MEMRI) after systemic injection of MnCl(2) could detect axonal sprouting in the hippocampus following kainate (KA) induced status epilepticus (SE). MEMRI was performed at 3 h, 25 h, 4 days, and 2 months post-SE. To assess the contribution of various cellular alterations that occur in parallel with sprouting to the MEMRI signal, we sacrificed animals for histology at 4 days and 2 months post-SE. Neurodegeneration was assessed from thionin and Fluoro-Jade B stained preparations, astrogliosis from GFAP (glial fibrillary acidic protein) and microgliosis from Ox-42 immunostained preparations. Sprouting of granule cells axons (mossy fibers) in the dentate gyrus was analyzed from Timm stained sections. Occurrence of spontaneous epileptic seizures was analyzed at 2 months post-SE using continuous video-EEG monitoring. Integrity of the blood-brain barrier (BBB) was studied using Gd-enhanced MRI. We found abnormal MEMRI hyperintensity in the CA1 and the dentate gyrus at 2 months post-SE but not at earlier time points. Based on histologic analysis of individual animals with MEMRI hyperintensity, hippocampal MEMRI changes could be attributed to increasing axonal density rather than to neurodegeneration, astrogliosis, or microgliosis. Moreover, MEMRI contrast was not affected by seizure activity, and we could not detect any leakage of the BBB that could have explained the observed MEMRI hyperintensity. Present data show that systemic MEMRI can reveal axonal sprouting, and thus, can potentially serve as a marker for neuroplasticity in preclinical studies.
[Show abstract][Hide abstract] ABSTRACT: The need to use animal models to develop imaging markers that could be linked to electrophysiological abnormalities in epilepsy and able to predict epileptogenicity in human studies is widely acknowledged. This study aimed to investigate the value of early magnetic resonance imaging (MRI) in predicting the long-term increased seizure susceptibility in the clinically relevant model of post-traumatic epilepsy (PTE). Moderate traumatic brain injury (TBI) was induced by lateral fluid-percussion in two groups of adult rats (34 injured, 16 controls). In Experiment 1, MRI follow-up was performed using a 4.7 T magnet at 3 h, 3 days, 9 days, 23 days, 2 months, 3 months and 6 months after TBI. T2 and 1/3 of the trace of the diffusion tensor (D(av)) were quantified from a single slice using a fast spin-echo sequence. In Experiment 2, MRI was performed at 7 and 11 months post-injury. In both groups, seizure susceptibility was tested by injecting a single dose of pentylenetetrazol at 12 months post-injury. Electrographic and behavioural responses were monitored for 1 h. Total number of spikes, total number of epileptiform discharges (EDs) and latency to first spike were measured. Finally, the severity of mossy fibre sprouting was evaluated. In both experiments, EEG parameters such as total number of spikes or EDs proved to be reliable indicators of increased seizure susceptibility in injured animals when compared to controls (P < 0.05). In the hippocampus ipsilateral to TBI, D(av) correlated with these EEG parameters at both early (3 h), and chronic (23 days, 2, 3, 6, 7 and 11 months) time points after TBI, as well as with the density of mossy fibre sprouting. These results for the first time demonstrate that quantitative diffusion MRI can serve as a tool to facilitate prediction of increased seizure susceptibility in a clinically relevant model of human PTE.
[Show abstract][Hide abstract] ABSTRACT: Epileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Introduction The MRI investigation of spatio-temporal changes in morphology and tissue water-homeostasis in traumatic brain injury (TBI) may clarify the mechanisms of TBI and provide an insight into long-term consequences leading to e.g. development of epilepsy in ~50 % of patients with penetrating head trauma. In the present study the evolution of quantitative MRI parameters in different brain regions were studied in fluid percussion induced TBI model for six months. M Me et th ho od ds s TBI was induced to 14 Spraque Dawley –rats by fluid percussion as previously described . 5 sham operated and 4 intact rats served as controls. MRI data were acquired in 4.7T Magnex magnet interfaced to Varian Inova console. Quadratur half volume rf-coil was used in transmit/receive –mode. Rats were anaesthetised with 1% halothane and MRI was performed 3 hours, 3 days, 9 days, 23 days, 2 months, 3 months and 6 months after induction of TBI. Volumetric changes were detected using T 2 -wt adiabatic spin echo multi-slice sequence (TE=70ms, TR=3s, 128*256pts, FOV 3*3cm 2 , thk=0.75mm, 19 slices covering rat cerebrum). T 2 , T 1ρ and the 1/3 of the trace of diffusion tensor (D av) were quantified from a single slice using a fast-spin-echo sequence (TR=3.0s, echo spacing=10ms, 16 echoes, 128*256pts, FOV=3*3cm 2 , thk=1.5mm; T2: TE=20, 38, 52, 76ms; T1ρ: spin lock times=18, 38, 58, 78ms, B1 SL =0.8G; diffusion: b-values=90, 496,1014s/mm²). Gradient echo –sequence (TE=5ms, 15ms, TR=0.7s, flip angle=20°) was used to detect intracerebral hemorrhage. Histological assessment of neuronal damage will be performed from Nissl stained sections corresponding to MRI slice. Results Volumetric changes: progression of the damage was evident from the increasing cortical lesion or/and the increased size of ipsilateral ventricle and the decreased size of hippocampus (Figs 1 and 2). There was a significant variation between individual animals and for initial analysis, rats were divided into 3 groups according to 23-day lesion+ventricle volume: 'severe' > 30 mm 3 > 'moderate' > 10 mm 3 > 'mild' (Fig.1). Hemorrhage: Most of the animals (11/14) had intracerebral hemorrhage in between ipsilateral cortex and hippocampus in acute phase, 3 hours after trauma, (Fig.2), and this seems to be related to development of lesion and/or severe atrophy (Fig.3). Fig. 1: Volumetric changes: (A) the sum of lesion and ipsilateral ventricle volumes and (B) the cross-section area of ipsilateral hippocampus. Fig 2. (A-C) T 2 -wt images showing progression of lesion in severe group and (D) a T 2 *-wt image demonstrating intracerebral hemorrhage. Fig.3: The intracerebral hemorrhage in acute phase and its correlation with the severity of lesion. Each arrow represents an individual animal. Cortical lesion area: All trauma animals displayed decreased D av in the ipsilateral cortical area at 3hrs (severe group 22%, moderate-group 9% and mild group 6% decrease compared to the sham operated controls, Table 1). This initial diffusion drop was followed by normalization and/or an increase of D av after day 9 to the level that was >300%, 25% or 0% of the control in severe, moderate and mild groups respectively. At 3 hours, T 1ρ was elevated by 15%, 8% and 2% and T 2 20%, 12% and 4% in severe, moderate and mild groups respectively. During subsequent weeks-months relaxation values in the severe-group dramatically increased being > 10 times higher than in controls from 2 months timepoint onwards. Relaxation times in moderate group peaked at day 3 (T 1ρ 26% and T 2 21% increase) stabilising to lower level (T 1ρ +12% and T 2 to +3%) in later timepoints Hippocampus: Both T 1ρ -and T 2 -times were elevated on day 3 in ipsilateral hippocampus (T 1ρ 8%, 8% and 5%; T 2 6%, 4% and 0% for severe, moderate and mild-groups, respectively). In subsequent measurements at days 9-23 relaxation times returned to the control level (T 1ρ) or slightly below (T 2). Interestingly, relaxation times showed secondary increase after 3 months. In T 2 this secondary increase levelled of at 5% above the control-level, but T 1ρ gradually increased throughout the rest of the 6-months observation period. In hippocampus D av showed no changes in acute or subacute phase but became elevated after 2 months. Table 1: Quantitative diffusion and relaxation values from ipsilateral cortex and hippocampus in moderate-group,(n=7, Mean ± SEM) Fig 4: T 1ρ and D av in ipsilateral hippocampus.
[Show abstract][Hide abstract] ABSTRACT: Prevention of epileptogenesis after brain insults, such as status epilepticus (SE), head trauma, or stroke, remains a challenge. Even if epilepsy cannot be prevented, it would be beneficial if the pathologic process could be modified to result in a less severe disease. We examined whether early discontinuation of SE reduces the risk of epilepsy or results in milder disease. Epileptogenesis was triggered with SE induced by electrical stimulation of the amygdala. Animals (n = 72) were treated with vehicle or diazepam (DZP, 20 mg/kg) 2 h or 3 h after the beginning of SE. Electrode-implanted non-stimulated rats served as controls for histology. All animals underwent continuous long-term video-electroencephalography monitoring 7-9 weeks and 11-15 weeks later to detect the occurrence and severity of spontaneous seizures. As another outcome measure, the severity of hippocampal damage was assessed in histologic sections. In the vehicle group, 94% of animals developed epilepsy. DZP treatment reduced the percentage of epileptic animals to 42% in the 2-h DZP group and to 71% in the 3-h DZP group (p < 0.001 and p < 0.05 compared to the vehicle group, respectively). If epilepsy developed, the seizures were less frequent in DZP-treated animals compared to the vehicle group (median 16.4 seizures/day), particularly in the 2-h DZP group (median 0.4 seizures/day). Finally, if DZP treatment was started 2 h, but not 3 h after SE, the severity of hippocampal cell loss was milder and the density of mossy-fiber sprouting was lower than in the vehicle group. These data indicate that treatment of SE with DZP within 2 h reduces the risk of epilepsy later in life, and if epilepsy develops, it is milder.
Epilepsy Research 01/2005; 63(1):27-42. DOI:10.1016/j.eplepsyres.2004.10.003 · 2.02 Impact Factor