Postnatal Changes in Local Cerebral Blood Flow Measured by the Quantitative Autoradiographic [¹⁴C]Iodoantipyrine Technique in Freely Moving Rats

Abstract

Summary:The postnatal changes in local cerebral blood flow in freely moving rats were measured by means of the quantitative autoradiographic e 4C]iodoantipyrine method. The animals were studied at 10, 14, 17, 21, and 35 days and at the adult stage. At 10 days after birth, rates of blood flow were very low and quite homogeneous in most cerebral structures except in a few posterior areas. From these relatively uniform levels, values of local ce rebral blood flow rose notably to reach a peak at 17 days in all brain regions studied. Rates of blood flow decreased between 17 and 21 days after birth and then increased from weaning time to reach the known characteristic dis tribution of the adult rat. The postnatal evolution of local cerebral blood flow in the rat is in good agreement with Local cerebral blood flow (LCBF) techniques have been extensively used to map changes in ce rebral metabolic rate in a variety of animal species including rat, cat, piglet, sheep, dog, monkey, and humans (Ca vazutti and Duffy, 1982; Flecknell et aI., 1983; Hascoet et aI. , 1988; Hosokawa et aI. , 1977; Kennedy et aI., 1972;Lassen and Ingvar, 1972; Plotkine et aI., 1986; Raichle et aI. , 1983; Reivich et aI., 1968 Reivich et aI., , 1969 Rosenberg et aI. , 1982; Sakurada et aI. , 1978;Sokoloff, 1961). Indeed, it has been shown in adult animals that in most phys iological or pharmacological states, functional ac tivity in the different structures of the central ner vous system regulates the local rate of energy me tabolism and that LCBF is coupled to local metabolic demand (Des Rosiers et aI., 1974; McCulReceived December 12, 1988; revised March 30, 1989; ac cepted April 7, 1989 579previous studies in other species such as dog and humans that also show higher rates of cerebral blood flow and glucose utilization at immature stages. However, in the rat, local cerebral blood flow and local cerebral glucose utilization are not coupled over the whole postnatal pe riod studied, since blood flow rates reach peak values at 17 days whereas glucose utilization remains still quite low at that stage. The high rate of cerebral blood flow in the 17-day-old rat may reflect the energetic and biosynthetic needs of the actively developing brain that are completed by the summation of glucose and ketone body utilization. Reivich, 1974;Sokoloff, 1961Sokoloff, , 1981. Studies performed in immature dogs (Gre goire et aI. , 1978) and in human infants and children (Chugani and Phelps, 1986; Chugani et aI., 1987;Kennedy and Sokoloff, 1957) were also able to show that, in newborns as in adults, cerebral blood flow and metabolism are tightly coupled.The e4C]iodoantipyrine autoradiographic method of Sakurada et al. (1978) requires catheterization of blood vessels in order to permit administration of the tracer and to facilitate collection of timed arte rial blood samples. For these reasons, this tech nique has been mostly used in animals of a quite large size such as adult rats (Ingvar et aI., 1981; McCulloch et aI. , 1982; Mraovitch et aI. , 1986) or c...

Metabolic Maturation of the Brain: A Study of Local Cerebral Glucose Utilization in the Developing Cat

“…A bimodal pattern of the ICBF developmental curve was also observed by Nehlig et al (1989) dur ing postnatal maturation in the rat; this study found that, following an initial peak lCBF at 17 days, a decline in ICBF occurred in many structures between 17 and 21 days, after which there was a sec ond increase in lCBF to reach final adult values. This second increase in lCBF in the rat, however, consisted of a gradual increase from 21 days to ap proach adult values by 35 days.…”

“…It is probably for this reason that a transient developmental stage of increased ICMRglc over adult values was not de tected in the developing rat in the study by Nehlig et al (1988). More recent studies by Nehlig et al (1989) suggest that measurements of local cerebral blood flow (lCBF) are a better indicator of total ce rebral energy demand in the immature rat than lCMRglc measurements.…”

“…This second increase in lCBF in the rat, however, consisted of a gradual increase from 21 days to ap proach adult values by 35 days. Since sexual matu rity in the rat is reached by about 50 to 60 days (Tilney, 1933) and ICBF determinations were not performed between 35 days and the adult stage in the study by Nehlig et al (1989), it is possible that a similar second peak in ICBF occurring at about 50 to 60 days may have been missed. The issues of whether such a peak exists in the rat, as well as the biological significance of the second metabolic peak so clearly shown in the present study in the cat, merit further experimental consideration.…”

Dynamic Spatio-Temporal Imaging of Early Reflow in a Neonatal Rat Stroke Model

“…18,31 Compared with other studies, our CBF values are substantially higher than those reported in unanesthetized neonate rats. 10,31,32 Our methodological CBF procedure can hardly account for the differences, since it is very close to that of Nehlig et al 31 Basal hypercapnia found in P7 rats (62.4 ± 5.0 mm Hg), compared with juvenile (36 ± 2 mm Hg) and adult rats (38 ± 1 mm Hg) could in part explained the enhanced CBF values measured in this study, because arterial CO 2 was reported to increase cerebrocortical red-cell flow under moderate isoflurane anesthesia. 33 The caudorostral gradient of blood-flow rates we found in sham-operated p7 rats is steeper than that reported in other studies.…”

Local Cerebral Blood Flow in the Newborn Rabbit: An Autoradiographic Study of Changes during Development

“…The newborn rat, although economical, is so small at birth that it is not possible to catheterize vessels or obtain blood samples necessary to monitor physiologic changes that may influence the cerebral circulation. Nevertheless, techniques for autoradiographic cerebral blood flow measurements have been adapted for rats 7 or 10 d of age (5,6). The newborn lamb and piglet are of an appropriate size for frequent sampling of blood and recording of various physiologic parameters; however, these animals are rather large for extensive autoradiographic studies of cerebral blood flow.…”