2 results for Pathipati, P

  • Growth hormone and prolactin regulate human neural stem cell regenerative activity

    Pathipati, P; Gorba, T; Scheepens, A; Goffin, V; Sun, Y; Fraser, Mhoyra (2011)

    Journal article
    The University of Auckland Library

    We have previously shown that the growth hormone (GH)/prolactin (PRL) axis has a significant role in regulating neuroprotective and/or neurorestorative mechanisms in the brain and that these effects are mediated, at least partly, via actions on neural stem cells (NSCs). Here, using NSCs with properties of neurogenic radial glia derived from fetal human forebrains, we show that exogenously applied GH and PRL promote the proliferation of NSCs in the absence of epidermal growth factor or basic fibroblast growth factor. When applied to differentiating NSCs, they both induce neuronal progenitor proliferation, but only PRL has proliferative effects on glial progenitors. Both GH and PRL also promote NSC migration, particularly at higher concentrations. Since human GH activates both GH and PRL receptors, we hypothesized that at least some of these effects may be mediated via the latter. Migration studies using receptor-specific antagonists confirmed that GH signals via the PRL receptor promote migration. Mechanisms of receptor signaling in NSC proliferation, however, remain to be elucidated. In summary, GH and PRL have complex stimulatory and modulatory effects on NSC activity and as such may have a role in injury-related recovery processes in the brain.

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  • Relationship between evolving epileptiform activity and delayed loss of mitochondrial activity after asphyxia measured by near-infrared spectroscopy in preterm fetal sheep

    Bennet, Laura; Roelfsema, V; Pathipati, P; Quaedackers, JS; Gunn, Alistair (2006)

    Journal article
    The University of Auckland Library

    Early onset cerebral hypoperfusion after birth is highly correlated with neurological injury in premature infants, but the relationship with the evolution of injury remains unclear. We studied changes in cerebral oxygenation, and cytochrome oxidase (CytOx) using near-infrared spectroscopy in preterm fetal sheep (103???104 days of gestation, term is 147 days) during recovery from a profound asphyxial insult (n = 7) that we have shown produces severe subcortical injury, or sham asphyxia (n = 7). From 1 h after asphyxia there was a signi???cant secondary fall in carotid blood ???ow (P < 0.001), and total cerebral blood volume, as re???ected by total haemoglobin (P < 0.005), which only partially recovered after 72 h. Intracerebral oxygenation (difference between oxygenated and deoxygenated haemoglobin concentrations) fell transiently at 3 and 4 h after asphyxia (P < 0.01), followed by a substantial increase to well over sham control levels (P < 0.001). CytOx levels were normal in the ???rst hour after occlusion, was greater than sham control values at 2???3 h (P < 0.05), but then progressively fell, and became signi???cantly suppressed from 10 h onward (P < 0.01). In the early hours after reperfusion the fetal EEG was highly suppressed, with a superimposed mixture of fast and slow epileptiform transients; overt seizures developed from 8 ?? 0.5 h. These data strongly indicate that severe asphyxia leads to delayed, evolving loss of mitochondrial oxidative metabolism, accompanied by late seizures and relative luxury perfusion. In contrast, the combination of relative cerebral deoxygenation with evolving epileptiform transients in the early recovery phase raises the possibility that these early events accelerate or worsen the subsequent mitochondrial failure.

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