Locomotor Activity is a Predictive Test after Global Ischemia-Reperfusion in Mongolian Gerbils

Abstract

Objective: The Mongolian gerbil is one of the main animal species used for the study of global ischemia, due to its specific Circle of Willis. Because of their anatomic variations, a large number of animals is needed. On account of the specific vulnerability of the hippocampus, striatum and neocortex, it is possible to evaluate the severity of the ischemic damage through an analysis of locomotor activity. The tests support the sensitvity of the experimental sample and compensate the interanimal variability.

Methods: The locomotor pattern of 30 male Mongolian gerbils was recorded before they were subjected to experimental bilateral carotid clippage for 15 minutes followed by reperfusion. A transparent 75×50×90 cm acrylic box was filmed in order to determine the total distance covered by the animals in five minutes, for three consecutive days. The locomotor activity of the animals was also examined in an open field at 24 hours and seven days after ischemia. Serum neurospecific enolase (NSE) was measured in the ischemic group and compared with that of an intact control group.

Results: The recording for normal animals was uniformly similar (average 200 squares in periphery), in the first trial of 3 consecutive days (188±6.7 S.D.). After ischemia, the numbers increased to 388 (± 40 S.D.), indicating that they were sensitive to the ischemic episode. Seven days later they returned to basal values. Serum NSE was high in the ischemic group versus the intact control group (S=<0.001).

Conclusions: Locomotor activity in an open field is a useful reference as a predictive test to determine the sensitivity of experimental animals to ischemia. It is also associated to the degree of cerebral damage in global ischemia-reperfusion, and this behavior is representative of the expression of selective ischemic injury. The determination of NSE is useful as an associated parameter of ischemic injury.

Key words

Mongolian gerbil - locomotor hyperactivity - cerebral ischemia - hippocampus

References

• 1 Amano M, Hasegawa M, Hasegawa T, Nabeshima T. Characteristics of transient cerebral ischemia-induced deficits on various learning and memory tasks in male Mongolian gerbils.  Jpn J Pharmacol. 1993;  63 469-477
• 2 Chandler M, DeLeo J, Carney JM. An unanesthetized-gerbil model of cerebral ischemia-induced behavioral changes.  J Pharmacol Methods. 1985;  14 137-146
• 3 Mayevsky A, Breuer Z. Brain vasculature and mitochondrial responses to ischemia in gerbils. I. Basic anatomical patterns and biochemical correlates.  Brain Research. 1992;  598 242-250
• 4 Andersen MB, Zimmer J, Sams-Dodd F. Postischemic hyperactivity in the mongolian gerbil correlates with loss of hippocampal neurons.  Behavioral Neurosciences. 1997;  111 1205-1216
• 5 Kuroiowa T, Bonnekoh P, Hossmann KA. Locomotor hyperactivity and CA1 hippocampal injury after transient forebrain ischemia of gerbils.  Neuroscience Lett. 1991;  122 141-144
• 6 Kuroiowa T, Bonnekoh P, Hossmann KA. Therapeutic window of halothane anesthesia for reversal of delayed neuronal injury in gerbils; relationship to postischemic motor hyperactivity.  Brain Research. 1991;  563 33-38
• 7 Mitani A, Andou Y, Kataoka K. Selective vulnerability of hippocampal CA1 neurons cannot be explained in terms of an increase in glutamate concentration during ischemia in the gerbil: brain microdyalisis study.  Neuroscience. 1992;  48 307-313
• 8 Payan H M, Conrad JR. Carotid ligation in gerbils. Influence of age, sex, and gonads.  Stroke. 1977;  8 194-196
• 9 Stummer W, Weber K, Tranmer B, Baethmann A, Kempski O. Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia.  Stroke. 1994;  25 1862-1869
• 10 Tamura A, Kawai K, Takagi K. Animal models used in cerebral ischemia and stroke research. In: Horst T, Korf J (Eds), Clinical Pharmacology of Cerebral Ischemia. Humana Press, Totowa 1977: 265-294
• 11 Urban L, Neill KH, Crain BJ, Nadler JV, Somjen GG. Postischemic synaptic physiology in area CA1 of the hippocampus studied in vitro.  J Neurosci. 1989;  9 3966-3975
• 12 Wang D, Corbett D. Cerebral ischemia, locomotor activity and spatial mapping.  Brain Res. 1990;  533 ((1)) 78-82
• 13 Weber K, Baethmann A, Kempski O. Determinants of survival after forebrain ischemia in Mongolian Gerbils.  Metab Brain Dis. 1988;  3 247-255
• 14 Yamada K, Hayakawa T, Yoshimine T, Ushio Y. A New model of transient hindbrain ischemia in gerbils.  J Neurosurg. 1984;  60 1054-1058
• 15 Yamamoto M, Takahashi K, Yamaguchi T, Saitoh S, Yatsugi S, Kogure K. Behavioral and histological changes after repeated brief cerebral ischemia by carotid artery occlusion in gerbils.  Brain Res. 1993;  608 16-20
• 16 Madhusree M. Trends in animal research.  Scientific American. 1997;  276 ((2)) 70-77
• 17 Mayevsky A. Level of ischemia and brain functions in the Mongolian gerbil in vivo.  Brain Res. 1990;  524 ((1)) 1-9
• 18 Horn M, Seger F, Schlote W. Neuron-specific enolase in gerbil brain and serum after transient cerebral ischemia.  Stroke. 1995;  26 290-297
• 19 Hardemark H, Eericsson N, Kotwica Z, Rundstrom G, Hartvig M, Olsson Y, Phalman S, Persson L. S-100 protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage.  J Neurosurg. 1989;  71 727-731
• 20 Antonawich FJ, Melton CS, Wu P, Davis JN. Nesting and shredding behavior as an indicator of hippocampal ischemic damage.  Brain Res. 1997;  764 ((1-2)) 249-252
• 21 Araki H, Nojiri M, Kawashima K, Kimura M, Aihara H. Behavioral, electroencephalographic and histopatological studies on mongolian gerbils with occluded common carotid arteries.  Physiol Behav. 1986;  38 89-94
• 22 Babcock AM, Baker DA, Lovec R. Locomotor activity in the ischemic gerbil.  Brain Res. 1993;  625 351-354
• 23 Mayevsky A, Kaplan H, Haveri J, Haselgrove J, Chance B. Three-dimensional metabolic mapping of the freeze trapped brain: effects of ischemia in the Mongolian gerbil.  Brain Res. 1986;  367 ((1-2)) 63-72
• 24 Gadamski R, Kroh H. Immunoreactivity of astroglia after brief ischemia resulting in asymmetrical damage to the hippocampal CA1 sector in the Mongolian gerbil.  Folia Neuropathol. 1994;  32 95-99
• 25 Gerhardt SC, Boast CA. Motor activity changes following cerebral ischemia in gerbils are correlated with the degree of neuronal degeneration in hippocampus.  Behav Neurosci. 1988;  102 301-303, 328
• 26 Berry K, Wisniewski HM, Svarzvein L, Baez S. On the relationship of brain vasculature to production of neurological deficit and morphological changes following acute unilateral common carotid artery ligation in gerbils.  J Neurol Sci. 1975;  25 75-92
• 27 Breuer Z, Mayevsky A. Brain vasculature and mitochondrial responses to ischemia in gerbils. II. Strain differences and statistical evaluation.  Brain Res. 1992;  598 251-256
• 28 Canevari L, Console A, Tendi EA, Clark JB, Bates TE. Effect of postischaemic hypotermia on the mitocondrial damage induced by ischaemia and reperfusion in the gerbil.  Brain Res. 1999;  817 241-245
• 29 Colbourne F, Auer RN, Sutherland GR. Characterization of postischemic behavioral deficits in gerbils with and without hypotermic neuroprotection.  Brain Res. 1998;  803 69-78
• 30 Imai F, Sawada M, Suzuki H, Zlokovic BV, Kojima J, Kuno S, Nagatsu T, Nitatori T, Uchiyama Y, Kanno T. Exogenous microglia anter the brain and migrate into ichaemic hippocampal lesions.  Neurosci Lett. 1999;  272 127-130
• 31 Karasawa Y, Araki H, Otomo S. Changes in locomotor activity and passive avoidance task performance induced by cerebral ischemia in Mongolian gerbils.  Stroke. 1994;  25 645-650
• 32 Katsuta K, Umemura K, Ueyama N, Matsuoka N. Pharmacological evidence for a correlation between hippocampal CA1 cell damage and hyperlocomotion following global cerebral ischemia in gerbils.  Eur J Pharmacol. 2003;  467 103-109
• 33 Kitagawa K, Matsumoto M, Handa N, Fukunaga R, Ueda H, Isaka Y, Kimura K, Kamada T. Prediction of stroke-prone gerbils and their cerebral circulation.  Brain Res. 1989;  479 263-269
• 34 Corbett D, Crooks P. Ischemic preconditioning: a long term survival study using behavioral and histological endpoints.  Brain Res. 1977;  760 129-136

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