A long-term video-EEG and behavioral follow-up after endothelin-1 induced middle cerebral artery occlusion in rats

Karhunen, Heli; Nissinen, Jari; Sivenius, Juhani; Jolkkonen, Jukka; Pitkänen, Asla

doi:10.1016/j.eplepsyres.2006.07.003

Cited by 32 publications

(26 citation statements)

References 39 publications

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“…Electrographic seizures have been reported in aged animals months following a photothrombotic lesion (Kelly et al, 2001;Kelly, 2002). Chronic spontaneous motor seizures have generally not been identified in other stroke models (Karhunen et al 2003(Karhunen et al , 2006. Though recently it has been reported by Karhunen et al (2007) that rats do develop motor seizures after a cortical photothrombotic lesion in a proportion of animals similar to what was observed in this study.…”

Section: Epilepsysupporting

confidence: 70%

“…Occlusion of the middle cerebral artery or photothrombotic-induced injury leads to both gross and histopathological injury in the neocortex, but the hippocampus is spared (for a full review of the models see Ginsberg and Busto, 1989). None of the above models have demonstrated chronic spontaneous motor seizures, although electrographic abnormalities have been seen (Kelly et al, 2001;Kelly, 2002;Karhunen et al 2003Karhunen et al , 2006Epsztein et al, 2006). These observations led to the hypothesis that both hippocampal and neocortical injury may potentiate the generation of chronic motor seizures in rodents.…”

mentioning

confidence: 98%

“…Factors associated with ischemic brain injury and epilepsy are poorly defined, but it appears that large cortical lesions have a strong association with the later appearance of seizures (Berges et al, 2000;Lamy et al, 2003). Currently, the occurrence of chronic spontaneous recurrent motor seizures have been observed in only one rodent model of focal ischemia (cortical photothrombosis, Karhunen et al 2007), but not in focal ischemia induced by middle cerebral artery occlusion (Karhunen et al 2003(Karhunen et al , 2006 nor in global ischemia (Epsztein et al, 2006).Global forebrain ischemia following cardiopulmonary arrest in humans has been shown to cause delayed hippocampal neuronal loss (Petito et al, 1987). The rodent model commonly used to analyze this type of brain injury is the four-vessel occlusion model Brierley, 1979, Pulsinelli et al, 1982).…”

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confidence: 99%

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A chronic histopathological and electrophysiological analysis of a rodent hypoxic–ischemic brain injury model and its use as a model of epilepsy

Williams¹,

Dudek

2007

Neuroscience

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Ischemic brain injury is one of the leading causes of epilepsy in the elderly, and there are currently no adult rodent models of global ischemia, unilateral hemispheric ischemia, or focal ischemia that report the occurrence of spontaneous motor seizures following ischemic brain injury. The rodent hypoxic-ischemic (H-I) model of brain injury in adult rats is a model of unilateral hemispheric ischemic injury. Recent studies have shown that an H-I injury in perinatal rats causes hippocampal mossy fiber sprouting and epilepsy. These experiments aimed to test the hypothesis that a unilateral H-I injury leading to severe neuronal loss in young-adult rats also causes mossy fiber sprouting and spontaneous motor seizures many months after the injury, and that the mossy fiber sprouting induced by the H-I injury forms new functional recurrent excitatory synapses. The right common carotid artery of 30-day old rats was permanently ligated, and the rats were placed into a chamber with 8% oxygen for 30 min. A quantitative stereologic analysis revealed that the ipsilateral hippocampus had significant hilar and CA1 neuronal loss compared to the contralateral and sham-control hippocampi. The septal region from the ipsilateral and contralateral hippocampus had small but significantly increased amounts of Timm staining in the inner molecular layer compared to the sham-control hippocampi. Three of 20 lesioned animals (15%) were observed to have at least one spontaneous motor seizure 6-12 months after treatment. Approximately 50% of the ipsilateral and contralateral hippocampal slices displayed abnormal electrophysiological responses in the dentate gyrus, manifest as all-or-none bursts to hilar stimulation. This study suggests that H-I injury is associated with synaptic reorganization in the lesioned region of the hippocampus, and that new recurrent excitatory circuits can predispose the hippocampus to abnormal electrophysiological activity and spontaneous motor seizures. KeywordsEpilepsy; sprouting; recurrent excitation; population spikes; epileptiform bursts Correspondence to: F. Edward Dudek, Ph.D. Department of Physiology, University of Utah School of Medicine, 420 Chipeta Way, Suite 1700, Salt Lake City, UT 84108, (801) 587-5880, ed.dudek@hsc.utah.edu. 1 Current address: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH; 2 Current address: Department of Physiology, University of Utah School of Medicine, Salt Lake City, UT.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; ...

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Section: Epilepsysupporting

confidence: 70%

mentioning

confidence: 98%

mentioning

confidence: 99%

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A chronic histopathological and electrophysiological analysis of a rodent hypoxic–ischemic brain injury model and its use as a model of epilepsy

Williams¹,

Dudek

2007

Neuroscience

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“…In the present study, epileptic animals demonstrated alterations in NPY IR in both cortex and hippocampus; however, the significance of these changes is not known at present. The absence of mossy fiber sprouting in either the inner molecular layer of the dentate gyrus or in the mossy fiber terminal region of CA3 pyramidal cells may be related to the absence of an initial, induced episode of status epilepticus following focal ischemia (Karhunen et al, 2006;Kelly et al, 2001;Kharlamov et al, 2003); the latter has yet to be validated with long-term monitoring studies using cortical and hippocampal electrodes. However, the present study reveals some of the transient and/or long-lasting changes of NPY expression demonstrated in other models of acute seizures or epilepsy (Gall et al, 1990;Tonder et al, 1994;Vezzani et al, 2000;Vezzani and Sperk, 2004).…”

Section: Discussionmentioning

confidence: 99%

Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis

Kharlamov

Kelly

2007

Brain Research

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This study characterized morphological changes in the cortex and hippocampus of Sprague-Dawley rats following photothrombotic infarction and epileptogenesis with emphasis on the distribution of neuropeptide Y (NPY) expression. Animals were lesioned in the left sensorimotor cortex and compared with age-matched naïve and sham-operated controls by immunohistochemical techniques at 1, 3, 7, and 180 days post-lesioning (DPL). NPY immunostaining was assessed by light microscopy and quantified by the optical fractionator technique using unbiased stereological methods. At 1, 3, and 7 DPL, the number of NPY-positive somata in the lesioned cortex was increased significantly compared to controls and the contralateral cortex. At 180 DPL, lesioned epileptic animals with frequent seizure activity demonstrated significant increases of NPY expression in the cortex, CA1, CA3, hilar interneurons, and granule cells of the dentate gyrus. In addition to NPY immunostaining, neuronal degeneration, cell death/cell loss, and astroglial response were assessed with cell-specific markers. Nissl and NeuN staining showed reproducible infarctions at each investigated time point. FJB-positive somata were most abundant in the infarct core at 1 DPL, decreased markedly at 3 DPL, and virtually absent by 7 DPL. Activated astroglia were detected in the cortex and hippocampus following lesioning and the development of seizure activity. In summary, NPY protein expression and morphological changes following cortical photothrombosis were time-, region-and pathologic state-dependent. Alterations in NPY expression may reflect reactive or compensatory responses of the rat brain to acute infarction and to the development and expression of epileptic seizures.

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“…The acquisition deficit observed in the groups receiving the two largest doses of ET-1 is comparable to previous research on stroke and spatial memory. Middle cerebral artery occlusion causes damage to the hippocampus and select cortical areas and can produce impairment on both acquisition and retention of platform location in the water maze task (Markgraf et al, 1992;Yonemori et al, 1996;Luo et al, 2007, but see Karhunen et al 2006). This deficit on the water maze task following stroke can be improved by treatment with anti-inflammatory drugs (Liu et al, 2006), voluntary wheel running (Luo et al, 2007) or enriched environment (Dahlquist et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Revisiting the cholinergic hypothesis in the development of Alzheimer's disease

Craig

Hong

McDonald

2011

Neuroscience & Biobehavioral Reviews

410

263

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Alzheimer's disease (AD) is the most common form of dementia affecting the elderly population today; however, there is currently no accurate description of the etiology of this devastating disorder. No single factor theory has been demonstrated as being causative; however, an alternative theory suggests that the interaction of multiple risk factors is responsible for AD. In this thesis I present data suggesting a neuroprotective role for acetylcholine during aging. Using a rat model of cholinergic depletion of the medial septum, I explored the effects of four common risk factors for AD (stress, seizures, stroke and circadian dysfunction) targeted at the hippocampus and examined the effects on measures of hippocampal dependent (water maze) and hippocampal independent (fear conditioning) memory. Here, I propose a role for acetylcholinemediated compensatory mechanisms in the functional recovery observed following sub threshold insults similar to those commonly observed in the elderly. m First and foremost I would like to thank my supervisor, Dr. Robert McDonald. Thank you for your support and encouragement, and for allowing me the independence to pursue my own projects and to learn from my experiences. I would also like to thank Nhung Hong for doing the majority of the cholinergic depletion and stroke surgeries used in this thesis and for teaching me the techniques. I would like to give a huge thank you to Joelle Kopp who was an invaluable asset who assisted in histology and spent many hours on the microscope counting cholinergic neurons. I would also like to thank Dr. Christine Werk for patiently reading and re-reading early drafts of my papers and this thesis and Dr.Hugo Lehmann for all his help in running statistics and interpreting my data. In addition, many thanks go out to Courtney Lamb, Robert Court and Arthur Verhoef for helping me with histology and behavioural testing, to Keri Colwell for running the corticosterone assays, the Metz lab for kindly allowing me the use of their microscope and to Karen Dow-Cazel and the rest of the animal care staff for taking care of my rats and helping me set up the circadian experiements. The cholinergic hypothesis of Alzheimer's disease 6 Acknowledgements IVThe basal forebrain cholinergic system 8The role of the basal forebrain cholinergic system in learning and memory 10The current state of the cholinergic hypothesis of Alzhimer's disease 15Risk factors for Alzheimer's disease 16Multiple combinations of co-factors theory of Alzheimer's disease 22The role of the hippocampus in learning and memory 24Objective of the present thesis 25Chapter 2: A series of pilot studies to determine the threshold for behaviourally sub threshold stroke, seizures and stress 28Abstract 29Experiment la: The effect of a chronic variable stress schedule on performance of the water maze task 32 Materials and Methods 33Results 36Experiment lb: The effects of a variable restraint stress procedure on levels of blood borne CORT 39 Materials and Methods 39Results 40Discussion 41Experiment 2: T...

show abstract

A long-term video-EEG and behavioral follow-up after endothelin-1 induced middle cerebral artery occlusion in rats

Cited by 32 publications

References 39 publications

A chronic histopathological and electrophysiological analysis of a rodent hypoxic–ischemic brain injury model and its use as a model of epilepsy

A chronic histopathological and electrophysiological analysis of a rodent hypoxic–ischemic brain injury model and its use as a model of epilepsy

Changes in neuropeptide Y protein expression following photothrombotic brain infarction and epileptogenesis

Revisiting the cholinergic hypothesis in the development of Alzheimer's disease

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