Combination treatment with ethyl pyruvate and IGF-I exerts neuroprotective effects against brain injury in a rat model of neonatal hypoxic-ischemic encephalopathy

Dysfunctional cerebrovascular autoregulation may contribute to neurologic injury in neonatal hypoxic-ischemic encephalopathy (HIE). Identifying the optimal mean arterial blood pressure (MAPopt) that best supports autoregulation could help identify hemodynamic goals that support neurologic recovery. In neonates who received therapeutic hypothermia for HIE, we hypothesized that the wavelet hemoglobin volume index (wHVx) would identify MAPopt and that blood pressures closer to MAPopt would be associated with less brain injury on MRI. We also tested a correlation-derived hemoglobin volume index (HVx) and single- and multi-window data processing methodology. Autoregulation was monitored in consecutive 3-h periods using near infrared spectroscopy in an observational study. The neonates had a mean MAP of 54 mmHg (standard deviation: 9) during hypothermia. Greater blood pressure above the MAPopt from single-window wHVx was associated with less injury in the paracentral gyri (p = 0.044; n = 63), basal ganglia (p = 0.015), thalamus (p = 0.013), and brainstem (p = 0.041) after adjustments for sex, vasopressor use, seizures, arterial carbon dioxide level, and a perinatal insult score. Blood pressure exceeding MAPopt from the multi-window, correlation HVx was associated with less injury in the brainstem (p = 0.021) but not in other brain regions. We conclude that applying wavelet methodology to short autoregulation monitoring periods may improve the identification of MAPopt values that are associated with brain injury. Having blood pressure above MAPopt with an upper MAP of ~50–60 mmHg may reduce the risk of brain injury during therapeutic hypothermia. Though a cause-and-effect relationship cannot be inferred, the data support the need for randomized studies of autoregulation and brain injury in neonates with HIE.

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hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in a Neonatal HIE Rat Model

Cell Transplantation ◽

10.1177/0963689719874769 ◽

2019 ◽

Vol 28 (12) ◽

pp. 1552-1559 ◽

Cited By ~ 1

Author(s):

Jianwei Xu ◽

Zhanhui Feng ◽

Xianyao Wang ◽

Ying Xiong ◽

Lan Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Umbilical Cord ◽

Rat Model ◽

Caspase 3 ◽

Neuroprotective Effect ◽

Hypoxic Ischemic Encephalopathy ◽

Human Umbilical Cord ◽

Motor Functions ◽

Ischemic Encephalopathy

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.

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Induced Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy: Pathophysiology, Current Treatment, and Nursing Considerations

Neonatal Network The Journal of Neonatal Nursing ◽

10.1891/0730-0832.30.1.29 ◽

2011 ◽

Vol 30 (1) ◽

pp. 29-36 ◽

Cited By ~ 10

Author(s):

DeLinda Jo Cooper

Keyword(s):

Brain Injury ◽

Healing Process ◽

Current Treatment ◽

Therapeutic Interventions ◽

Hypoxic Ischemic Encephalopathy ◽

Second Phase ◽

Induced Hypothermia ◽

Compensatory Mechanism ◽

Neuroprotective Strategy ◽

Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE) can lead to devastating neurodevelopmental consequences such as cerebral palsy, seizure disorders, and significant developmental delays. HIE in the newborn is often the result of a hypoxic event, such as uterine rupture, placental abruption, or cord prolapse. Biphasic brain injury occurs in HIE. The first phase involves activation of the sympathetic nervous system as a compensatory mechanism. The second phase, known as reperfusion brain injury, occurs hours later. Induced hypothermia, a neuroprotective strategy for treating HIE, targets the second phase to prevent reperfusion injury. NICU nurses are in a unique position to detect patient instability and to maintain the therapeutic interventions that contribute to the healing process. This article highlights the significant role nurses play in the management of infants diagnosed with HIE who are treated with induced hypothermia.

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Late failure of cerebral autoregulation in hypoxic-ischemic encephalopathy is associated with brain injury: a pilot study

Physiological Measurement ◽

10.1088/1361-6579/aae54d ◽

2018 ◽

Vol 39 (12) ◽

pp. 125004 ◽

Cited By ~ 5

Author(s):

Zachary A Vesoulis ◽

Steve M Liao ◽

Amit M Mathur

Keyword(s):

Brain Injury ◽

Pilot Study ◽

Cerebral Autoregulation ◽

Hypoxic Ischemic Encephalopathy ◽

Late Failure ◽

Ischemic Encephalopathy

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Comparison of Chemical Exchange Saturation Transfer Imaging with Diffusion-weighted Imaging and Magnetic Resonance Spectroscopy in a Rat Model of Hypoxic-ischemic Encephalopathy

Magnetic Resonance in Medical Sciences ◽

10.2463/mrms.mp.2019-0128 ◽

2020 ◽

Vol 19 (4) ◽

pp. 359-365 ◽

Cited By ~ 1

Author(s):

Akiko Ohki ◽

Shigeyoshi Saito ◽

Eri Hirayama ◽

Yusuke Takahashi ◽

Yuko Ogawa ◽

...

Keyword(s):

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Rat Model ◽

Diffusion Weighted Imaging ◽

Chemical Exchange ◽

Hypoxic Ischemic Encephalopathy ◽

Chemical Exchange Saturation Transfer ◽

Resonance Spectroscopy ◽

Saturation Transfer ◽

Ischemic Encephalopathy

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Current Controversies in Newer Therapies to Treat Birth Asphyxia

International Journal of Pediatrics ◽

10.1155/2011/848413 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Pia Wintermark

Keyword(s):

Brain Injury ◽

Neurological Outcome ◽

Mild Hypothermia ◽

Birth Asphyxia ◽

Hypoxic Ischemic Encephalopathy ◽

Monitoring Technology ◽

The Past ◽

Neuroprotective Strategy ◽

Ischemic Encephalopathy

Despite major advances in monitoring technology and knowledge of fetal and neonatal pathophysiology, neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the main causes of severe adverse neurological outcome in children. Until recently, there were no therapies other than supportive measures. Over the past several years, mild hypothermia has been proven to be safe to treat HIE. Unfortunately, this neuroprotective strategy seems efficient in preventing brain injury in some asphyxiated newborns, but not in all of them. Thus, there is increasing interest to rapidly understand how to refine hypothermia therapy and add neuroprotective or neurorestorative strategies. Several promising newer treatments to treat birth asphyxia and prevent its devastating neurological consequences are currently being tested. In this paper, the physiopathology behind HIE, the currently available treatment, the potential alternatives, and the next steps before implementation of these other treatments are reviewed.

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