title: Nanoscale intracortical iron injection induces chronic epilepsy in rodent.
abstract: We studied the electrophysiological, hemodynamic, and cytomorphological consequences of microhemorrhagic brain injury induced by a nanoscale iron injection. Of particular interest were the etiology, development, and treatment of epilepsy associated with this injury. We developed an animal model of chronic epilepsy using nanoscale injection into the adult mouse cortex. Although injection of nanoamounts of iron did not cause clear cell death or damage in the cortex, it elicited varying degrees of spontaneous epileptiform events that could be recorded under anesthesia 3 months postinjection. The influence of these chronic epileptiform events on neurovascular coupling was probed by directly stimulating the cortex ipsilateral to the epileptic focus and by measuring cerebral blood volume simultaneously in both hemispheres using intrinsic signal optical imaging. The ipsilateral hemodynamic response was dramatically lower in animals that exhibited longer, more frequent epileptiform events, but it was unchanged in animals displaying infrequent, short events. In contrast, the contralateral hemodynamic response was augmented in all iron-injected animals compared with the control group. These abnormal hemodynamic responses in chronically epileptic animals were correlated with the degree of reduction in the number of GABAergic interneurons. Therefore, nanoscale iron injection, which mimics some aspects of microhemorrhagic brain injury, generated chronic, yet varying, degrees of spontaneous epileptiform events. Moreover, the severity of the epileptiform events corresponded to the degree of reduction in GABAergic interneurons in the iron-injected hemisphere and the level of autoregulatory dysfunction of cerebral blood flow. © 2013 Wiley Periodicals, Inc.
authors.affiliation: Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Sungkyunkwan University, Suwon 440-746, Republic of Korea; Department of Biological Science, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Jo
authors.forename: Chaejeong
authors.initials: C
authors.lastname: Heo
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Schwartz
authors.forename: Minah
authors.initials: M
authors.lastname: Suh
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000494:pharmacology*; D002452:Cell Count; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004827:Epilepsy / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000494:pharmacology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D020300:Intracranial Hemorrhages / Q000209:etiology; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010320:Parvalbumins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D005296:Ferrous Compounds; D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
keywords: GABAergic interneuron hemodynamics; epilepsy; in vivo optical imaging; microhemorrhage