Granule Cell Neurogenesis After Status Epilepticus in the Immature Rat Brain

Sankar, Raman; Shin, Don; Liu, Hantao; Katsumori, Hiroshi; Wasterlain, Claude G.

doi:10.1111/j.1528-1157.2000.tb01557.x

Cited by 84 publications

(66 citation statements)

References 21 publications

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“…Animals underwent pilocarpine-induced SE at P20 and BrdU injection to label dividing cells 4, 6, and 8 days later. We chose to inject during these times to capture the period of robust DGC division after pilocarpine-induced seizures (14,17). We then killed animals over the next 3 weeks to assess the survival of the newborn DGCs during the latent period, but be-…”

Section: Resultsmentioning

confidence: 99%

“…Dramatic increase in the birth of DGCs, seen after an episode of pilocarpine-induced SE, has been demonstrated by others in pilocarpine, kainate, and kindling models, in both adult and immature animals (14,15,17,25). We previously found a ∼20% increase in DGC numbers in adult animals that developed epilepsy after SE at P20, suggesting a possible persistence of DGCs born in the weeks after SE (24).…”

Section: Discussionmentioning

confidence: 99%

“…Multiple types of seizures have been shown to modify the birth rate of DGCs, increasing the rate from one to as much as tenfold (14)(15)(16)(17), although also see (18). Along with the increase in the birth of newborn DGCs, an increase of injured and dying DGCs also occurs after status epilepticus (SE) (19,20).…”

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Fate of Newborn Dentate Granule Cells after Early Life Status Epilepticus

2003

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Summary:Purpose: To determine the fate of newborn dentate granule cells (DGCs) after lithium-pilocarpine-induced status epilepticus (SE) in an immature rat.Methods: Postnatal day 20 (P20) rats were injected with lithium and pilocarpine to induce SE, and then with bromodeoxyuridine (BrdU) 4, 6, and 8 days later (P24, 26, and 28), and killed 1 day (P29), 1 week (P34), and 3 weeks (P50) after the last dose of BrdU for cell counts. Immunohistochemistry and TUNEL staining were performed to assess the fate of newborn DGCs.Results: Pilocarpine-treated animals had significantly more BrdU-labeled DGCs than did littermate controls at all times. The day after the final BrdU injection (P29), sixfold more cells were found in pilocarpine-treated animals than in controls, which was reduced to threefold, 3 weeks later. A decrease in the BrdUlabeled cell density was noted from P29 to P50 in the control and pilocarpine-treated animals. Evidence of DGC cell death was seen in pilocarpine and control animals, with threefold more TUNEL-positive cells in the pilocarpine-treated than in the control animals at P29. The surviving newborn DGCs became mature neurons; expressing the neuronal marker NeuN in both control and pilocarpine-treated animals.Conclusions: These findings suggest that SE during postnatal development increases the birth and death of DGCs. A subset of the newborn DGCs survive and mature into dentate granule neurons, resulting in an increased population of immature DGCs after SE that may affect hippocampal physiology. Key Words: Neurogenesis-Cell death-Hippocampus-Status epilepticus.The generation of a large number of new neurons throughout life is a distinctive feature of the hippocampal dentate gyrus (DG) (1,2). Limited studies have suggested that immature dentate granule cells (DGCs) have unique physiologic properties, and the birth of new DGCs is necessary for the establishment of certain types of memory in the rodent (3-5). As the total numbers of DGCs do not increase throughout life, a concomitant loss of DGCs must occur. The gradual loss of DGCs over weeks to months has been demonstrated in several species; however, why certain cells die is not well understood (6,7).Several growth factors have been implicated in DG neurogenesis (8-10), and alterations in the environment, drugs, hormones, age, and seizures all influence the rate of neurogenesis (11)(12)(13)(14). Multiple types of seizures have been shown to modify the birth rate of DGCs, increasing the rate from one to as much as tenfold (14-17), although also see (18). Along with the increase in the birth of newborn DGCs, an increase of injured and dying DGCs (19,20). Many of the dying cells are found at the dentate/hilar border, the area of DGC birth, suggesting that immature DGCs may be particularly susceptible to dying, although the number and phenotype of the dying cells has not been extensively characterized. Because SE increases both the birth and death rate of DGCs, it remains unclear how many newborn DGCs survive long after SE and thus could contribute to...

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fate of Newborn Dentate Granule Cells after Early Life Status Epilepticus

2003

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“…This appears to occur after brief seizures, 9 kindling, 60,71,92 and after status epilepticus induced by chemoconvulsants such as pilocarpine 26,73 or kainic acid 45, 69 or status epilepticus induced by electrical stimulation. 82 Seizures following electroconvulsive shock also increase neurogenesis. 64,93 Other experimental insults that injure the brain cause increased neurogenesis also, such as experimental trauma or stroke.…”

Section: Introductionmentioning

confidence: 99%

Functional Implications of Seizure-Induced Neurogenesis

Scharfman¹

2004

Advances in Experimental Medicine and Biology

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The neurobiological doctrine governing the concept of neurogenesis has undergone a revolution in the past few years. What was once considered dubious is now well accepted: new neurons are born in the adult brain. Science fiction is quickly becoming a reality as scientists discover ways to convert skin, bone, or blood cells into neurons.In the epilepsy arena, widespread interest has developed because of the evidence that neurogenesis increases after seizures, trauma, and other insults or injuries that alter seizure susceptibility.This review discusses some of the initial studies in this field, and their often surprising functional implications. The emphasis will be on the granule cells of hippocampus, because they are perhaps more relevant to epilepsy than other areas in which neurogenesis occurs throughout life, the olfactory bulb and subventricular zone. In particular, the following questions will be addressed:

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“…In mature rats, animal studies have confirmed that single episode of status epilepticus induced by pilocarpine [2] , kainic acid [3] and kindling [4] can increase cell proliferation in the subgranular zone of the dentate gyrus, cause neuronal loss in the hippocampus, and lead to aberrant sprouting of mossy fibers in the pyramidal cell region of CA3 and the supragranular zone of dentate gyrus. In immature rat, previous researches [5][6] have manifested that a prolonged seizure resulted in more neurogenesis but less cell loss and sprouting than it did in adult. However, other studies have demonstrated that neonatal seizures resulted in reduced neurogenesis [7][8] .…”

Section: Introductionmentioning

confidence: 96%

Morphological and behavioral consequences of recurrent seizures in neonatal rats are associated with glucocorticoid levels

et al. 2007

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Objective It is well documented that epilepsy can increase neurogenesis in certain brain regions and cause behavioral alternations in patients and different epileptic animal models. A series of experimental studies have demonstrated that neurogenesis is regulated by various factors including glucocorticoid (CORT), which can reduce neurogenesis. Most of studies in animal have been focused on adulthood stage, while the effect of recurrent seizures to immature brain in neonatal period has not been well established. This study was designed to investigate how the recurrent seizures occurred in the neonatal period affected the immature brain and how CORT regulated neurogenesis in immature animals. Methods Neonatal rats were subjected to 3 pilocarpine-induced seizures from postnatal day 1 to day 7. Then neurogenesis at different postnatal ages (i.e. P8, P12, P22, P50) was observed. Behavioral performance was tested when the rats were mature (P40), and plasma CORT levels following recurrent seizures were simultaneously monitored. Results Rats with neonatal seizures had a significant reduction in the number of Bromodeoxyuridine (BrdU) labeled cells in the dentate gyrus compared with the control groups when the animals were euthanized on P8 or P12 (P < 0.05); whereas there was no difference between the two groups on P22. Until P50, rats with neonatal seizures had increased number of BrdU-labeled cells compared with the control group (P < 0.05). In Morris water maze task, pilocarpine-treated rats were significantly slower than the control rats at the first and second day, and there were no differences at other days. In probe trial, there was no significant difference in time spent in the goal quadrant between the two groups. Endocrine studies showed a correlation between the number of BrdU positive cells and the CORT level. Sustained increase in circulating CORT levels was observed following neonatal seizures on P8 and P12. Conclusion Neonatal recurrent seizures can biphasely modulate neurogenesis over different time windows with a down-regulation at early time and up-regulation afterwards, cause persistent deficits in cognitive functions of adults, and increase the circulating CORT levels. CORT levels are related with the morphological and behavioral consequences of recurrent seizures.

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Granule Cell Neurogenesis After Status Epilepticus in the Immature Rat Brain

Cited by 84 publications

References 21 publications

Fate of Newborn Dentate Granule Cells after Early Life Status Epilepticus

Fate of Newborn Dentate Granule Cells after Early Life Status Epilepticus

Functional Implications of Seizure-Induced Neurogenesis

Morphological and behavioral consequences of recurrent seizures in neonatal rats are associated with glucocorticoid levels

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