DOI: http://dx.doi.org/10.18203/issn.2454-2156.IntJSciRep20162806

Pentylenetetrazol-induced seizures strength in diabetic and normal serum glucose elevated male mice

Mohsen Khalili, Zahra Kiasalari, Payman Raise Abdullahi

Abstract


Background: Epilepsy is one of the most important neurological disorders, afflicting both genders during their lifetime. Metabolic disturbances, including hyperglycemia and hypoglycemia, are one of the main reasons of seizures in which frequently have been seen in diabetes mellitus. A large body of literature has investigated correlation between hyperglycemia, hypoglycemia and seizure. However, a definitive conclusion has not been taken, yet. Hence, we developed a rodent model of PTZ-induced seizure in order to investigate about relation between PTZ-induced seizures and glycemic changes, including diabetic and non-diabetic hyperglycemia and hypoglycemia.

Methods: We chose 50 naive, adult male inbred mice of the Balb/c strain (aged 8–10 weeks, weighted 25-35 grams) and divided them into 5 groups, randomly (n=10 in each groups): 1. Control (received saline and citrate buffer). 2. Diabetic group (received STZ 140 mg/kg I.P). 3. Diabetic+Glibenclamide group (received STZ 140 mg/kg I.P and treated with Glibenclamide 1 mg/kg I.P daily). 4. Non-diabetic hyperglycemic group (received glucose "D-dextrose" 2 g/kg I.P 30 min before PTZ administration. 5. Hypoglycemic group (the animals were fasted one day other days during experimental period). Chemical kindling was induced by PTZ injection (35 mg/kg, I.P), every other days (11 periods that lasted 22 days).  

Results: Our data shown non-diabetic hyperglycemic mice that had elevated blood glucose levels, were more resistant to seizures compared to control group (p<0.05). Threshold and duration of the second phase of the seizures in non-diabetic hyperglycemic mice were increased (p<0.001). Moreover, threshold of the phase 5 was enhanced (p<0.001). Again, hypoglycemic mice had statistically significant decrease in threshold of phase 5 compared to control group (p<0.05).

Conclusions: We found that acute non-diabetic hyperglycemia not only have had no aggravating effects on seizure susceptibility but also have shown anticonvulsive effects. As well, we found that hypoglycemia has decreased threshold of phase 5 in challenge dose, i.e. onset of the most severe phase of the seizures was accelerated.

Keywords


PTZ, Diabetic, Seizure, Glucose mice

Full Text:

PDF

References


Bell GS, Sander JW. The epidemiology of epilepsy: the size of the problem. Seizure. 2002;11:306-14.

Theodore WH, Fisher R. Brain stimulation for epilepsy. Acta Neurochir Suppl. 2007;97:261-72.

Theodore WH, Spencer SS, Wiebe S, Langfitt JT, Ali A, Shafer PO, et al. Epilepsy in North America: a report prepared under the auspices of the global campaign against epilepsy, the International Bureau for Epilepsy, the International League Against Epilepsy, and the World Health Organization. Epilepsia. 2006;47(10):1700-22.

Gorji A, Khaleghi Ghadiri M. History of epilepsy in Medieval Iranian medicine. Neurosci Biobehav Rev. 2001;25(5):455-61.

Shin C, McNamara JO. Mechanism of epilepsy. Annu Rev Med. 1994;45:379-89.

Köhling R. Voltage-gated sodium channels in epilepsy. Epilepsia. 2002;43(11):1278-95.

Khaleghi Ghadiri M, Gorji A. Natural remedies for impotence in medieval Persia. Int J Impot Res. 2004;16(1):80-3.

Schwechter EM, Veliskova J, Velisek L. Correlation between extracellular glucose and seizure susceptibility in adult. Ann Neurol. 2003;53(1):91-101.

Reid CA, Kim TH, Berkovic SF, Petrou S. Low blood glucose precipitates spike-and-wave activity in genetically predisposed. Epilepsia. 2011;52(1): 115-20.

Huang CW, Tsai JJ, Ou HY, Wang ST, Cheng JT, Wu SN, et al. Diabetic hyperglycemia is associated with the severity of epileptic seizures in adults. Epilepsy Res. 2008;79(1):71-7.

Huang CW, Cheng JT, Tsai JJ, Wu SN, Huang CC. Diabetic hyperglycemia aggravates seizures and status epilepticus-induced hippocampal damage. Neurotox Res. 2009;15(1):71-81.

Lin TN, Te J, Huang HC, Chi SI, Hsu CY. Prolongation and enhancement of postischemic c-fos expression after fasting. Stroke. 1997;28(2):412-8.

Marie C, Bralet AM, Gueldry S, Bralet J. Fasting prior to transient cerebral ischemia reduces delayed neuronal necrosis. Metab Brain Dis. 1990;5(2):65-75.

Sapolsky RM, Stein BA. Status epilepticus-induced hippocampal damage is modulated by glucose availability. Neurosci Lett. 1989;97(1-2):157-62.

Schauwecker PE. The effects of glycemic control on seizures and seizure-induced excitotoxic cell death. BMC Neurosci. 2012;13:94-8.

Chen JW, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol. 2006:5;246-56.

Szyndler J, Rok P, Maciejak P, Walkowiak J, Czlonkowska AI, Sienkiewicz-Jarosz H, et al. Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems. Pharmacol Biochem Behav. 2002;73(4):851-61.

Ghasemi M, Shafaroodi H, Karimollah AR, Gholipour T, Nezami BG, Ebrahimi F, et al. ATP-sensitive potassium channels contribute to the time-dependent alteration in. Seizure. 2010;19(1):53-8.

Dong J, Peeters TL, De Smet B, Moechars D, Delporte C, Vanden Berghe P, et al. Role of endogenous ghrelin in the hyperphagia of mice with streptozotocin-induced. Endocrinology. 2006;147(6):2634-42.

Yazar A, Polat G, Un I, Levent A, Kaygusuz A, Buyukafsar K, et al. Effects of glibenclamide, metformin and insulin on the incidence and latency of. Pharmacol Res. 2002;45(3):183-7.

Wójcicka G, Jamroz-Wiśniewska A, Marciniak A, Łowicka E, Bełtowski J. The differentiating effect of glimepiride and glibenclamide on paraoxonase 1 and platelet-activating factor acetylohydrolase activity. Life Sci. 2010;87(3):126-32.

Yang Z, Laubach VE, French BA, Kron IL. Acute hyperglycemia enhances oxidative stress and exacerbates myocardial. J Thorac Cardiovasc Surg. 2009;137(3):723-9.

Reid CA, Kim TH, Berkovic SF, Petrou S. Low blood glucose precipitates spike-and-wave activity in genetically predisposed animals. Epilepsia. 2011;52(1):115-20.

Johansen FF, Diemer NH. Influence of the plasma glucose level on brain damage after systemic kainic acid injection in the rat. Acta Neuropathol. 1986;71(1-2):46-54.

Choi DW. Calcium and excitotoxic neuronal injury. Ann N Y Acad Sci. 1994;747:162-71.

Proks P, Reimann F, Green N, Gribble F, Ashcroft F. Sulfonylurea stimulation of insulin secretion. Diabetes. 2002;51(3):368-76.

Seino S, Miki T. Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol. 2003;81(2):133-76.

Iadarola MJ, Gale K. Substantia nigra: site of anticonvulsant activity mediated by gamma-aminobutyric acid. Science. 1982;218(4578):1237-40.

Depaulis A, Vergnes M, Marescaux C. Endogenous control of epilepsy: the nigral inhibitory system. Prog Neurobiol. 1994;42(1):33-52.

Grabauskas G, Song I, Zhou S, Owyang C. Electrophysiological identification of glucose-sensing neurons in rat nodose ganglia. J Physiol. 2010;588:617-32.

Levin BE, Routh VH, Kang L, Sanders NM, Dunn-Meynell AA. Neuronal glucosensing: what do we know after 50 years. Diabetes. 2004;53(10):2521-8.

Burdakov D, Luckman SM, Verkhratsky A. Glucose-sensing neurons of the hypothalamus. Philos Trans R Soc Lond B Biol Sci. 2005;360(1464):2227-35.

Song Z, Levin BE, McArdle JJ, Bakhos N, Routh VH. Convergence of pre- and postsynaptic influences on glucosensing neurons in the ventromedial hypothalamic nucleus. Diabetes. 2001;50(12):2673-81.

Routh VH. Glucose-sensing neurons: are they physiologically relevant. Physiol Behav. 2002;76(3):403-13.

Oomura Y, Ooyama H, Sugimori M, Nakamura T, Yamada Y. Glucose inhibition of the glucose-sensitive neurone in the rat lateral hypothalamus. Nature. 1974;247(439):284-6.

Fioramonti X, Contié S, Song Z, Routh VH, Lorsignol A, Pénicaud L. Characterization of glucosensing neuron subpopulations in the arcuate nucleus: integration in neuropeptide Y and pro-opio melanocortin networks. Diabetes. 2007;56(5):1219-27.

Burdakov D, Jensen LT, Alexopoulos H, Williams RH, Fearon IM, O'Kelly I, et al. Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose. Neuron. 2006;50(5):711-22.

Burdakov D, Lesage F. Glucose-induced inhibition: how many ionic mechanisms. Acta Physiol. 2010;198(3):295-301.

de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci. 1998;95(1):322-7.

Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(5):696-9.

Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, et al. Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci. 1998;18(23):9996-10015.

Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, et al. Fos expression in orexin neurons varies with behavioral state. J Neurosci. 2001;21(5):1656-62.

Kiyashchenko LI, Mileykovskiy BY, Maidment N, Lam HA, Wu MF, John J, et al. Release of hypocretin (orexin) during waking and sleep states. J Neurosci. 2002;22(13):5282-6.

Taylor MM, Samson WK. The other side of the orexins: endocrine and metabolic actions. Am J Physiol Endocrinol Metab. 2003;284(1):13-7.

Siegel JM. Hypocretin (orexin): role in normal behavior and neuropathology. Annu Rev Psychol. 2004;55:125-48.

Harnish MJ, Greenleaf SR, Orr WC. A comparison of feeding to cephalic stimulation on postprandial sleepiness. Physiol Behav. 1998;64(1):93-6.

Muroya S, Uramura K, Sakurai T, Takigawa M, Yada T. Lowering glucose concentrations increases cytosolic Ca2+ in orexin neurons of the rat lateral hypothalamus. Neurosci Lett. 2001;309(3):165-8.

Yamanaka A, Beuckmann CT, Willie JT, Hara J, Tsujino N, Mieda M, et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003;38(5):701-13.

Bittencourt JC, Presse F, Arias C, Peto C, Vaughan J, Nahon JL, et al. The melanin-concentrating hormone system of the rat brain: an immuno- and hybridization histochemical characterization. J Comp Neurol. 1992;319(2):218-45.

Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature. 1998;(396):670-4.