The functional organization of the hippocampal dentate gyrus and its relevance to the pathogenesis of temporal lobe epilepsy

Annals of Neurology - Tập 35 Số 6 - Trang 640-654 - 1994
Robert S. Sloviter1,2
1Departments of Pharmacology and Neurology, College of Physicians and Surgeons of Columbia University, New York, NY
2Neurology Research Center, Helen Hayes Hospital, New York State Department of Health, West Haverstraw, NY

Tóm tắt

AbstractTemporal lobe seizures are frequently associated with a characteristic pattern of hippocampal pathology (hippocampal sclerosis), as well as pathology in other temporal lobe structures. Despite more than a century of study, the relationship between pathology and epileptogenesis remains unclear. Endfolium sclerosis, which is characterized by the loss of dentate hilar neurons that are presumed to govern dentate granule cell excitability, is evident whenever hippocampal sclerosis exists and is the only temporal lobe pathology in some patients. Because prolonged seizures or head trauma produce endfolium sclerosis and granule cell hyperexictability in experimental animals, hilar neuron loss may be the common pathological denominator and primary network defect underlying development of a hippocampal seizure “focus.” Physiological studies suggest that vulnerable hilar mossy cells normally excite neurons that mediate granule cell inhibition. Recent anatomical studies indicate that the axons of mossy cells project longitudinally, out of the lamellar plane in which their cell bodies lie. If mossy cells in one lamella excite inhibitory neurons in surrounding lamellae, neocortical excitation of one segment of the granule cell layer may produce lateral inhibition and limit neocortical excitation to the targeted lamella. In patients who have had status epilepticus, prolonged febrile seizures, head trauma, or encephalitis, loss of dentate mossy cells may deafferent inhibitory neurons, render them “dormant,” and thereby disinhibit an encephalitis, loss of dentate mossy cells may deafferent inhibitory neurons, render them “dormant,” and thereby disinhibit an enlarged expanse of the granule cell layer. The selective loss of neurons that normally govern lateral inhibition in the dentate gyrus may cause functional delamination of the granule cell layer and result in synchronous, multilamellar discharges in response to cortical stimuli. Repetitive seizures may ultimately produce the full pattern of hippocampal and mesial temporal sclerosis by destroying cells within the seizure circuit that were not injured irreversibly by the initial insult. Thus, hippocampal pathology may be both the cause and effect of seizures that originate in the temporal lobe.

Từ khóa


Tài liệu tham khảo

10.1093/brain/60.4.377

10.1001/archneurpsyc.1951.02320030009002

10.1007/BF02224538

10.1007/BF02047162

10.1093/brain/89.3.499

Meldrum BS, 1992, Greenfield's neuropathology, 1246

Bruton CJ, 1988, The neuropathology of temporal lobe epilepsy

10.1001/archneur.1968.00480040019001

10.1007/978-3-642-86299-1

10.1007/BF02878571

10.1007/BF02870249

10.1007/BF01814225

Gloor P, 1991, Epilepsy surgery, 689

Lüders HO, 1991, Epilepsy surgery, 51

Primrose DC, 1991, Epilepsy surgery, 601

Spencer DD, 1991, Epilepsy surgery, 533

10.3171/jns.1992.76.5.0735

10.1212/WNL.40.1.74

Babb TL, 1987, Surgical treatment of the epilepsies, 511

10.1002/cne.903080306

10.1126/science.2879352

10.1002/hipo.450010106

10.1097/00005072-196007000-00009

10.1001/archneur.1973.00490190028002

10.1038/271676a0

Olney JW, 1976, Acute dendrotoxic changes in the hippocampus of kainate treated rats, Brain Res, 76, 91

10.1016/0006-8993(80)90316-9

Olney JW, 1984, Excitotoxins, 82

10.1093/brain/101.4.687

10.1038/244442a0

10.1016/0304-3940(81)90171-3

10.1016/0361-9230(83)90037-0

10.1016/0361-9230(85)90059-0

10.1002/cne.901820508

10.1111/j.1748-1716.1966.tb03223.x

10.1016/0006-8993(78)90463-8

deLanerolle NC, 1988, Evidence for hippocampal interneuron loss in human temporal lobe epilepsy, Epilepsia, 29, 674

10.1016/0006-8993(89)90234-5

10.1523/JNEUROSCI.09-07-02562.1989

10.1016/0006-8993(89)91012-3

Williamson A, 1990, Intracellular recordings from epileptic human dentate granule cells show evidence of hyperexcitability, Epilepsia, 31, 625

10.1523/JNEUROSCI.12-12-04846.1992

10.1002/hipo.450040108

10.1002/cne.901050305

10.1007/BF01170832

10.1016/0006-8993(81)90413-3

10.1016/0006-8993(87)90301-5

Tomasulo RA, 1993, Activity‐mediated changes in feed‐forward inhibition in the dentate commissural pathway: relationship to EPSP/spike dissociation in the converging perforant path, J Neurophysiol, 69, 165, 10.1152/jn.1993.69.1.165

10.1152/jn.1982.48.3.597

10.1002/cne.902190304

10.1016/0006-8993(90)90930-A

Zimmer J, 1983, Neurobiology of the hippocampus, 39

10.1002/hipo.450020103

10.1007/BF01148116

10.1126/science.8093417

10.1002/cne.902560105

10.1007/BF00247498

Sloviter RS, 1989, The hippocampus—new vistas, 443

10.1002/cne.902900409

10.1002/cne.903000312

10.1007/BF00234087

10.1016/0306-4522(89)90424-7

10.1016/0306-4522(90)90100-I

10.1016/0006-8993(78)91113-7

Buckmaster PS, 1993, Interneurons and inhibition in the dentate gyrus of the rat in vivo, Soc Neurosci Abstr, 19, 351

Eccles JC, 1973, The understanding of the brain

DeVries SH, 1993, Synaptic circuitry of the retina and olfactory bulb, Neuron, 10, 139

10.1016/0014-4886(83)90080-8

10.1016/0006-8993(93)90917-C

10.1152/jn.1969.32.5.663

10.1139/y79-218

10.1016/0301-0082(89)90009-9

10.1016/S0079-6123(08)63112-X

10.1152/jn.1989.61.3.501

10.1001/archneur.1964.00460150003001

10.1016/0014-4886(92)90168-P

10.1001/archneur.1985.04060100040017

10.1016/0920-1211(93)90083-J

10.1111/j.1460-9568.1993.tb00508.x

10.1016/0006-8993(90)91601-C

10.1002/ana.410260303

10.1523/JNEUROSCI.05-04-01016.1985

10.1523/JNEUROSCI.11-09-02795.1991

10.1016/0006-8993(92)90777-7

10.1016/0304-3940(92)90306-R

Thông tin
Thông tin xuất bản

Annals of Neurology

Tập 35 Số 6

640-654

Thông tin tác giả