Bench to Cribside: the Path for Developing a Neuroprotectant

TY - JOUR

T1 - Bench to Cribside: the Path for Developing a Neuroprotectant

AU - Ramanantsoa, Nelina

AU - Fleiss, Bobbi

AU - Bouslama, Myriam

AU - Matrot, Boris

AU - Schwendimann, Leslie

AU - Cohen-Salmon, Charles

AU - Gressens, Pierre

AU - Gallego, Jorge

PY - 2013/4

Y1 - 2013/4

N2 - The consequences of perinatal brain injury include immeasurable anguish for families and substantial ongoing costs for care and support of effected children. Factors associated with perinatal brain injury in the preterm infant include inflammation and infection, and with increasing gestational age, a higher proportion is related to hypoxic-ischemic events, such as stroke and placental abruption. Over the past decade, we have acquired new insights in the mechanisms underpinning injury and many new tools to monitor outcome in perinatal brain injury in our experimental models. By embracing these new technologies, we can expedite the screening of novel therapies. This is critical as despite enormous efforts of the research community, hypothermia is the only viable neurotherapeutic, and this procedure is limited to term birth and postcardiac arrest hypoxic-ischemic events. Importantly, experimental and preliminary data in humans also indicate a considerable therapeutic potential for melatonin against perinatal brain injury. However, even if this suggested potential is proven, the complexity of the human condition means we are likely to need additional neuroprotective and regenerative strategies. Thus, within this review, we will outline what we consider the key stages of preclinical testing and development for a neuroprotectant or regenerative neurotherapy for perinatal brain injury. We will also highlight examples of novel small animal physiological and behavioral testing that gives small animal preclinical models greater clinical relevance. We hope these new tools and an integrated bench to cribside strategic plan will facilitate the fulfillment of our overarching goal, improving the long-term brain health and quality of life for infants suffering perinatal brain injury.

AB - The consequences of perinatal brain injury include immeasurable anguish for families and substantial ongoing costs for care and support of effected children. Factors associated with perinatal brain injury in the preterm infant include inflammation and infection, and with increasing gestational age, a higher proportion is related to hypoxic-ischemic events, such as stroke and placental abruption. Over the past decade, we have acquired new insights in the mechanisms underpinning injury and many new tools to monitor outcome in perinatal brain injury in our experimental models. By embracing these new technologies, we can expedite the screening of novel therapies. This is critical as despite enormous efforts of the research community, hypothermia is the only viable neurotherapeutic, and this procedure is limited to term birth and postcardiac arrest hypoxic-ischemic events. Importantly, experimental and preliminary data in humans also indicate a considerable therapeutic potential for melatonin against perinatal brain injury. However, even if this suggested potential is proven, the complexity of the human condition means we are likely to need additional neuroprotective and regenerative strategies. Thus, within this review, we will outline what we consider the key stages of preclinical testing and development for a neuroprotectant or regenerative neurotherapy for perinatal brain injury. We will also highlight examples of novel small animal physiological and behavioral testing that gives small animal preclinical models greater clinical relevance. We hope these new tools and an integrated bench to cribside strategic plan will facilitate the fulfillment of our overarching goal, improving the long-term brain health and quality of life for infants suffering perinatal brain injury.

KW - UMBILICAL-CORD OCCLUSION

KW - PERINATAL ASPHYXIA

KW - INHALED NITRIC-OXIDE

KW - NEONATAL INTENSIVE-CARE

KW - Neuroprotectant

KW - IMMATURE RAT-BRAIN

KW - WHITE-MATTER INJURY

KW - Behavioral testing

KW - FETAL SHEEP

KW - HYPOXIC-ISCHEMIC ENCEPHALOPATHY

KW - RESPIRATORY-DISTRESS-SYNDROME

KW - Preclinical

KW - Melatonin

KW - WHOLE-BODY HYPOTHERMIA

U2 - 10.1007/s12975-012-0233-2

DO - 10.1007/s12975-012-0233-2

M3 - Literature review

SN - 1868-4483

VL - 4

SP - 258

EP - 277

JO - Translational stroke research

JF - Translational stroke research

IS - 2

ER -