Effects of Pentylenetetrazol-Induced Status Epilepticus on Local Cerebral Blood Flow in the Developing Rat

The quantitative autoradiographic [14C]-iodoantipyrine technique was applied to measure the effects of a 30-min period of pentylenetetrazol (PTZ)-induced status epilepticus (SE) on local cerebral blood flow (LCBF) in rats 10 (P10), 14 (P14), 17 (P17), and 21 (P21) days after birth. The animals received repetitive, timed injections of subconvulsive doses of PTZ until SE was reached. At P10, SE induced a 32 to 184% increase in the rates of LCBF affecting all structures studied. In P14- and P17 PTZ-treated rats, LCBF values significantly increased in two-thirds of the structures belonging to all systems studied and were not changed by SE in the parietal cortex, dorsal hippocampus, and dentate gyrus. At P21, rates of LCBF were still increased in 48 of the 73 structures studied; however, LCBF values were decreased by SE in most cortical areas, the hippocampus, and the dentate gyrus. CBF and cerebral metabolic rate for glucose (CMRglc) remained coupled in both controls and PTZ-exposed rats. Our results show that changes in LCBF with seizures are age dependent. At the most immature ages, P10 and P14, both LCBF and local CMRglc (LCMRglc) values are largely increased by long-lasting seizures. At P17 and P21, the blood flow response to SE becomes more heterogeneous, with specific decreases in the hippocampus and cortex at P21. The absence of mismatch between LCBF and LCMRglc in PTZ-exposed rats at all ages may explain at least partly why the immature brain is more resistant to seizure-induced brain damage than the adult brain.

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Local Cerebral Blood Flow during Lithium–Pilocarpine Seizures in the Developing and Adult Rat: Role of Coupling between Blood Flow and Metabolism in the Genesis of Neuronal Damage

Journal of Cerebral Blood Flow & Metabolism ◽

10.1097/00004647-200202000-00007 ◽

2002 ◽

Vol 22 (2) ◽

pp. 196-205 ◽

Cited By ~ 42

Author(s):

Anne Pereira de Vasconcelos ◽

Arielle Ferrandon ◽

Astrid Nehlig

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Status Epilepticus ◽

Metabolic Rate ◽

Neuronal Damage ◽

Adult Brain ◽

Local Cerebral Blood Flow ◽

Adult Rats ◽

Flow Rates ◽

Cerebral Metabolic Rate

Coupling between local cerebral blood flow and local cerebral metabolic rate for glucose is involved in the pathogenesis of epilepsy-related neuronal damage in the adult brain; however, its role in the immature brain is unknown. Lithium–pilocarpine–induced status epilepticus is associated with extended damage in adult rats, mostly in the forebrain limbic areas and thalamus, whereas damage was moderate in 21-day-old rats (P21) or absent in P10 rats. The quantitative autoradiographic [14C]iodoantipyrine technique was applied to measure the consequences of lithium-pilocarpine status epilepticus on local cerebral blood flow. In adult and P21 rats, local cerebral blood flow rates increased by 50% to 400%; the highest increases were recorded in regions showing damage in adults. At P10, local cerebral blood flow rates decreased by 40% to 60% in most areas, except in some forebrain regions showing no change during status epilepticus. In areas injured when status epilepticus was induced in adults, a strong hypermetabolism ( Fernandes et al., 1999 ) not matched by comparable local cerebral blood flow increases was present in rats of all ages, whereas in damage-resistant areas, local cerebral metabolic rate for glucose and local cerebral blood flow remained coupled in the three age groups. Thus, the level of coupling between blood flow supply and metabolism is not involved in seizure-related brain damage in the developing brain, which appears to be resistant to the consequences of such a mismatch.

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Perivascular Microapplication of Endothelin-1: A New Model of Focal Cerebral Ischaemia in the Rat

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1993.108 ◽

1993 ◽

Vol 13 (5) ◽

pp. 865-871 ◽

Cited By ~ 164

Author(s):

John Sharkey

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Cerebral Ischaemia ◽

Dorsal Hippocampus ◽

Focal Cerebral Ischaemia ◽

Local Cerebral Blood Flow ◽

Guide Cannula ◽

Conscious Rat ◽

Endothelin 1 ◽

Arterial Blood

In the present study, we describe the effects of perivascular microapplication of the potent vasoconstrictor peptide endothelin-1 (Et-1; (120 pmol in 3 μl), delivered via a guide cannula stereotaxically positioned above the left cerebral artery (MCA) of the conscious male Sprague–Dawley rat. Ten minutes after the administration of Et-1, mean arterial blood pressure had increased by 20% and profound reductions in local cerebral blood flow (up to 93%) were observed within those brain areas supplied by the MCA. In addition, significant increases in local cerebral blood flow were observed within the globus pallidus (100%), substantia nigra pars reticulata (48%), ventrolateral thalamus (65%), and dorsal hippocampus (74%) ipsilateral to the insult. Twenty-four hours following the insult, the pattern of ischaemic damage was similar to that reported previously following permanent occlusion of the rat MCA. It is suggested that perivascular microapplication of Et-1 may provide a useful model for the study of the functional disturbances associated with focal cerebral ischaemia in the conscious rat.

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