Objective: Therapeutic hypothermia (HT) is the standard treatment for newborns after perinatal asphyxia. Preclinical studies report that HT is more effective when started early. Methods: Eighty cooled newborns were analyzed and grouped according to when cooling was started after birth: early (≤180 min) or late (>181 min). For survivors we analyzed whether starting cooling early was associated with a better psychomotor or mental developmental index (PDI or MDI, Bayley Scales of Infant Development II) than late cooling. Results: Forty-three newborns started cooling early and 37 started late. There was no significant difference in the severity markers of perinatal asphyxia between the groups; however, nonsurvivors (n = 15) suffered more severe asphyxia and had significantly lower centiles for weight (BWC; p = 0.009). Of the 65 infants that survived, 35 were cooled early and 30 were cooled late. There was no difference in time to start cooling between those who survived and those who did not. For survivors, median PDI (IQR) was significantly higher when cooled early [90 (77-99)] compared to being cooled later [78 (70-90); p = 0.033]. There was no increase in cardiovascular adverse effects in those cooled early. There was no significant difference in MDI between early and late cooling [93 (77-103) vs. 89 (76-106), p = 0.594]. Conclusion: Starting cooling before 3 h of age in surviving asphyxiated newborns is safe and significantly improves motor outcome. Cooling should be initiated as soon as possible after birth in eligible infants.

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We investigated the expression of metabotropic glutamate receptor (mGluR) isoforms in CG-4 rodent oligodendroglial progenitor cells (OPC) and rat brain oligodendrocytes. Our RT-PCR analysis detected mRNAs for mGluR3 and mGluR5 isoforms in OPCs. Although neurons express both mGluR5a and mGluR5b splice variants, only mGluR5a was identified in OPCs. Antibodies to mGluR2/3 and mGluR5 detected the corresponding receptor proteins in immunoblots of OPC membrane fractions. Furthermore, immunocytochemical analysis identified mGluR5 in oligodendrocyte marker O4-positive OPCs. The expression of mGluR5 was also demonstrated in oligodendrocyte marker (O4 and O1) positive cells in white matter of postnatal 4-and 7-day-old rat brain sections using immunofluorescent double labelling and confocal microscopy. The mGluR5 receptor function was assessed in CG-4OPCs with fura-2 microfluorometry. Application of the mGluR1/5 specific agonist (S)-3,5-dihydroxyphenylglycine (DHPG) induced calcium oscillations, which were inhibited by the selective mGluR5 antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). The DHPG induced calcium oscillations required Ca 2+ release from intracellular stores. InOPCs the group II mGluR agonist (2S,2¢R,3¢R)-2-(2¢,3¢-dicarboxycyclopropyl)glycine (DCG-IV) decreased forskolin-stimulated cAMP synthesis, indicating the presence of functional mGluR3. The newly identified mGluR3 and mGluR5a may be involved in the differentiation of oligodendrocytes, myelination and the development of white matter damage. Glutamate is the major excitatory neurotransmitter in the CNS and its responses are mediated by ionotropic (iGluRs) and metabotropic (mGluRs) glutamate receptors. The iGluRs mediate fast synaptic transmission and the mGluRs are involved in a variety of modulatory events associated with neuronal activity. The iGluRs are multimeric, cation-specific ion channels that are classified into three families on the basis of their pharmacology, electrophysiology and sequence homology: namely the a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptors (Dingledine et al. 1999). The mGluRs are G-protein coupled receptors, which mediate relatively slow responses to glutamate. There are eight mGluR genes (mGluR1-8) and these have been divided into three groups based on pharmacological, signal transduction and sequence similarities. Group I comprises mGluR1 and mGluR5, which are involved in the mobilization of intracellular calcium by stimulating phospholipase C and are activated by (S)-3,5-dihydroxyphenylglycine (DHPG). In group II, the mGluR2 and mGluR3 are typically linked to inhibition of adenylyl cyclase (AC) and react effectively with (2S,1¢S,2¢S)-2-(carboxycyclopropyl)glycine (DCG-IV). In group III, the mGluR4, mGluR6, mGluR7 and mGluR8 are linked to inhibition of cAMP formation by AC and respond effectively to L-2-amino-4-phosphonobutyrate (Conn and Pin 1997;Schoepp et al. 1999). Oligodendrocytes are responsible for axon myelination and they a...

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