Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy

Sokołowska, Paulina; Passemard, Sandrine; Mok, Amanda; Schwendimann, Leslie; Gozes, I.; Gressèns, Pierre

doi:10.1016/j.neuroscience.2010.10.074

Cited by 27 publications

(12 citation statements)

References 52 publications

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“…NAP has also shown protective activity in over 20 cell culture systems and in over 25 animal models. Notable examples include schizophrenia (36–38), Alzheimer’s disease (39–41), frontotemporal dementia (42, 43), amyotrophic lateral sclerosis (44), and most importantly cognitive deficiencies associated with ASD (5) as well as developmental delays linked to prenatal and postnatal toxicities (45–47). NAP, also called davunetide, has shown activity in clinical trials.…”

Section: Resultsmentioning

confidence: 99%

The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings

et al. 2017

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BackgroundActivity-dependent neuroprotective protein (ADNP) is one of the most prevalent de novo mutated genes in syndromic autism spectrum disorders, driving a general interest in the gene and the syndrome.AimThe aim of this study was to provide a detailed developmental case study of ADNP p.Tyr719* mutation toward improvements in (1) diagnostic procedures, (2) phenotypic scope, and (3) interventions.MethodsLongitudinal clinical and parental reports.ResultsAD (currently 11-year-old) had several rare congenital anomalies including imperforate anus that was surgically repaired at 2 days of age. Her findings were craniofacial asymmetries, global developmental delay, autistic behaviors (loss of smile and inability to make eye contact at the age of 15 months), and slow thriving as she gradually matures. Comprehensive diagnostic procedures at 3 years resulted in no definitive diagnosis. With parental persistence, AD began walking at 3.5 years (skipping crawling). At the age of 8.5 years, AD was subjected to whole exome sequencing, compared to the parents and diagnosed as carrying an ADNP p.Tyr719* mutation, a causal recurring mutation in ADNP (currently ~17/80 worldwide). Brain magnetic resonance imaging demonstrated mild generalized cerebral volume loss with reduced posterior white matter. AD is non-verbal, communicating with signs and word approximations. She continues to make slow but forward developmental progress, and her case teaches newly diagnosed children within the ADNP Kids Research Foundation.ConclusionThis case study emphasizes the importance of diagnosis and describes, for the first time, early motor intervention therapies. Detailed developmental profile of selected cases leads to better treatments.

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Section: Resultsmentioning

confidence: 99%

The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings

et al. 2017

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“…For example, NAP was able to block a variety of neuronal injuries (induced by electrical blockade, beta-amyloid peptide, or Apo-E deficiency) at the femtomolar level (Bassan et al, 1999). Further, NAP was effective at preventing diabetes-induced brain damage (Idan-Feldman et al, 2011) as well as ibotenic acid-induced excitotoxic injury in newborn mice (Sokolowska et al, 2011). The mechanism of action of NAP has not been fully determined but blocking the early stages of apoptosis from being engaged (Zemlyak et al, 2009c) and/or protecting the cytoskeleton from injury-induced breakdown are possible candidates (Zemlyak et al, 2009a, Zemlyak et al, 2009b).…”

Section: Discussionmentioning

confidence: 99%

Strategies to defeat ketamine-induced neonatal brain injury

Turner¹,

Gutiérrez²,

Li³

et al. 2012

Neuroscience

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Studies using animal models have shown that general anesthetics such as ketamine trigger widespread and robust apoptosis in the infant rodent brain. Recent clinical evidence suggests that the use of general anesthetics on young children (at ages equivalent to those used in rodent studies) can promote learning deficits as they mature. Thus, there is a growing need to develop strategies to prevent this injury. In this study, we describe a number of independent approaches to address therapeutic intervention. Postnatal day 7 (P7) rats were injected with vehicle (sterile PBS) or the NMDAR antagonist ketamine (20 mg/kg). At 8 hours after, we prepared brains for immunohistochemical detection of the pro-apoptotic enzyme activated caspase-3 (AC3). Focusing on the somatosensory cortex, AC3-positive cells were then counted in a non-biased stereological manner. We found AC3 levels were markedly increased in ketamine-treated animals. In one study, microarray analysis of the somatosensory cortex from ketamine-treated P7 pups revealed that expression of activity dependent neuroprotective protein (ADNP) was enhanced. Thus, we injected P7 animals with the ADNP peptide fragment NAP 15 min before ketamine administration and found we could dose-dependently reverse the injury. In separate studies, pretreatment of P6 animals with 20 mg/kg vitamin D3 or a non-toxic dose of ketamine (5 mg/kg) also prevented ketamine-induced apoptosis at P7. In contrast, pretreatment of P7 animals with aspirin (30 mg/kg) 15 min before ketamine administration actually increased AC3 counts in some regions. These data show that a number of unique approaches can be taken to address anesthesia-induced neurotoxicity in the infant brain, thus providing MDs with a variety of alternative strategies that enhance therapeutic flexibility.

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“…Interestingly, NAP was shown to have potent neuroprotective effects against ibotenate-induced excitotoxic damage in the cortical plate and the white matter of P5 mice [50] as well as in a model of neonatal hypoxic-ischemic insult [51]. NAP (generic name davunetide) has been used in clinical trials in patients suffering from amnestic mild cognitive impairment, a precursor to Alzheimer's disease, without significant side effect [52].…”

Section: Neuroprotective Properties Of Vip Deriva-tives and Clinical mentioning

confidence: 99%

VIP-induced Neuroprotection of the Developing Brain

Passemard¹,

Sokołowska²,

Schwendimann³

et al. 2011

Current Pharmaceutical Design

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Excitotoxicity is a key molecular mechanism of perinatal brain damage and is associated with cerebral palsy and long term cognitive deficits. VIP induces a potent neuroprotection against perinatal excitotoxic white matter damage. VIP does not prevent the initial appearance of white matter lesion but promotes a secondary repair with axonal regrowth. This plasticity mechanism involves an atypical VPAC2 receptor and BDNF production. Stable VIP agonists mimic VIP effects when given systemically and exhibit a large therapeutic window. Unraveling cellular and molecular targets of VIP effects against perinatal white matter lesions could provide a more general rationale to understand the neuroprotection of the developing white matter against excitotoxic insults.

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Neuroprotective effects of NAP against excitotoxic brain damage in the newborn mice: implications for cerebral palsy

Cited by 27 publications

References 52 publications

The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings

The Eight and a Half Year Journey of Undiagnosed AD: Gene Sequencing and Funding of Advanced Genetic Testing Has Led to Hope and New Beginnings

Strategies to defeat ketamine-induced neonatal brain injury

VIP-induced Neuroprotection of the Developing Brain

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