Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.

It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in yo...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Margaret Maheandiran, Shanthini Mylvaganam, Chiping Wu, Youssef El-Hayek, Sonia Sugumar, Lili Hazrati, Martin del Campo, Adria Giacca, Liang Zhang, Peter L Carlen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d35699abeb734ae6aa08ae857a835e88
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:d35699abeb734ae6aa08ae857a835e88
record_format	dspace
spelling	oai:doaj.org-article:d35699abeb734ae6aa08ae857a835e882021-11-18T08:39:57ZSevere hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.1932-620310.1371/journal.pone.0083168https://doaj.org/article/d35699abeb734ae6aa08ae857a835e882013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386156/?tool=EBIhttps://doaj.org/toc/1932-6203It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14-16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4 ± 1.3 mM) than in CON rodents (6.3 ± 0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8 ± 0.2 mM) and CON animals (1.6 ± 0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying mechanisms. Our data demonstrate that severe hypoglycemia (<2.0 mM) is a necessary precondition for seizures, and the increased frequency of these seizures is associated with mortality.Margaret MaheandiranShanthini MylvaganamChiping WuYoussef El-HayekSonia SugumarLili HazratiMartin del CampoAdria GiaccaLiang ZhangPeter L CarlenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e83168 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Margaret Maheandiran Shanthini Mylvaganam Chiping Wu Youssef El-Hayek Sonia Sugumar Lili Hazrati Martin del Campo Adria Giacca Liang Zhang Peter L Carlen Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
description	It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14-16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4 ± 1.3 mM) than in CON rodents (6.3 ± 0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8 ± 0.2 mM) and CON animals (1.6 ± 0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying mechanisms. Our data demonstrate that severe hypoglycemia (<2.0 mM) is a necessary precondition for seizures, and the increased frequency of these seizures is associated with mortality.
format	article
author	Margaret Maheandiran Shanthini Mylvaganam Chiping Wu Youssef El-Hayek Sonia Sugumar Lili Hazrati Martin del Campo Adria Giacca Liang Zhang Peter L Carlen
author_facet	Margaret Maheandiran Shanthini Mylvaganam Chiping Wu Youssef El-Hayek Sonia Sugumar Lili Hazrati Martin del Campo Adria Giacca Liang Zhang Peter L Carlen
author_sort	Margaret Maheandiran
title	Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
title_short	Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
title_full	Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
title_fullStr	Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
title_full_unstemmed	Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
title_sort	severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/d35699abeb734ae6aa08ae857a835e88
work_keys_str_mv	AT margaretmaheandiran severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT shanthinimylvaganam severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT chipingwu severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT youssefelhayek severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT soniasugumar severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT lilihazrati severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT martindelcampo severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT adriagiacca severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT liangzhang severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality AT peterlcarlen severehypoglycemiainajuvenilediabeticratmodelpresenceandseverityofseizuresareassociatedwithmortality
_version_	1718421529170018304

Severe hypoglycemia in a juvenile diabetic rat model: presence and severity of seizures are associated with mortality.

Ejemplares similares