Selective injury of thalamocortical tract in neonatal rats impairs forelimb use: model validation and behavioral effects.

Unilateral brain injury in neonates results in largely contralateral hand function in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury.

Targeted Infarction of the Internal Capsule in the Rat Using Microstimulation Guidance.

Background and Purpose- Lacunar strokes are subcortical infarcts with small size and high disability rates, largely due to injury of the corticospinal tract in the internal capsule (IC). Current rodent models of lacunar infarcts are created based on stereotactic coordinates. We tested the hypothesis that better understanding of the somatotopy of the IC and guiding the lesion with electrical stimulation would allow a more accurate lesion to the forelimb axons of the IC.

Corrigendum: Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

[This corrects the article DOI: 10.3389/fncir.2018.

Plasticity in One Hemisphere, Control From Two: Adaptation in Descending Motor Pathways After Unilateral Corticospinal Injury in Neonatal Rats.

After injury to the corticospinal tract (CST) in early development there is large-scale adaptation of descending motor pathways. Some studies suggest the uninjured hemisphere controls the impaired forelimb, while others suggest that the injured hemisphere does; these pathways have never been compared directly. We tested the contribution of each motor cortex to the recovery forelimb function after neonatal injury of the CST.

ZEB1 links p63 and p73 in a novel neuronal survival pathway rapidly induced in response to cortical ischemia.

Background: Acute hypoxic/ischemic insults to the forebrain, often resulting in significant cellular loss of the cortical parenchyma, are a major cause of debilitating injury in the industrialized world. A clearer understanding of the pro-death/pro-survival signaling pathways and their downstream targets is critical to the development of therapeutic interventions to mitigate permanent neurological damage.

Methodology/principal Findings: We demonstrate here that the transcriptional repressor ZEB1, thought to be involved in regulating the timing and spatial boundaries of basic-Helix-Loop-Helix transactivator-mediated neurogenic determination/differentiation programs, functions to link a pro-survival transcriptional cascade rapidly induced in cortical neurons in response to experimentally induced ischemia.

In vivo Neuroprotective Activity of Epopeptide AB Against Ischemic Damage.

Erythropoietin (Epo) is a hematopoietic factor, which stimulates proliferation and differentiation of erythroid precursor cells. Epo also functions as a neuroprotective factor and protects neurons from ischemic damage. Recently a 17-mer peptide sequence (Epopeptide AB) in Epo (AEHCSLNENITVPDTKV) with a neuroprotective function was reported.

Animal models of neonatal stroke and response to erythropoietin and cardiotrophin-1.

Neonatal stroke is increasingly recognized in preterm and term infants, and the rate of arterial ischemic infarction occurring around the time of birth is as high as the annual incidence of large-vessel ischemic stroke in adults. Thus, neonatal stroke is a major contributor to perinatal morbidity and mortality, and a considerable number of these children will develop long-term neurodevelopmental disabilities. Our ability to investigate this situation has been limited by the technical challenges in developing suitable animal models.

Intravenous infusion of dihydroginsenoside Rb1 prevents compressive spinal cord injury and ischemic brain damage through upregulation of VEGF and Bcl-XL.

Red ginseng root (Panax Ginseng CA Meyer) has been used clinically by many Asian people for thousands of years without any detrimental effects. One of the major components of Red ginseng root is ginsenoside Rb(1) (gRb1). Previously, we showed that intravenous infusion of gRb1 ameliorated ischemic brain damage through upregulation of an anti-apoptotic factor, Bcl-x(L) and that topical application of gRb1 to burn wound lesion facilitated wound healing through upregulation of vascular endothelial growth factor (VEGF).

Glucocorticoid receptor expression in the cortex of the neonatal rat brain with and without focal cerebral ischemia.

Background/aims: Glucocorticoid receptors (GR) mediate cellular processes which may be neuroprotective and/or neurotoxic to the neonatal rat brain. Our aim was to describe GR ontogeny in the developing rat brain cortex and changes in GR expression after permanent neonatal focal cerebral ischemia (FCI).

Methods: GR Western blots and immunohistochemical stains were performed on neonatal rat cortices on P1, P3, P7, P10, P15, and P30 and on P7 at 1 h, 3 h, 6 h, 12 h, 24 h, and 72 h after FCI or sham-operation (S-O), 8 per group.

Prevention of ischemic neuronal death by intravenous infusion of a ginseng saponin, ginsenoside Rb(1), that upregulates Bcl-x(L) expression.

Almost all agents that exhibit neuroprotection when administered into the cerebral ventricles are ineffective or much less effective in rescuing damaged neurons when infused into the blood stream. Search for an intravenously infusible drug with a potent neuroprotective action is essential for the treatment of millions of patients suffering from acute brain diseases. Here, we report that postischemic intravenous infusion of a ginseng saponin, ginsenoside Rb(1) (gRb(1)) (C(54)H(92)O(23), molecular weight 1109.

Mild intermittent hypoxia does not induce stress responses in the neonatal rat brain.

We previously demonstrated that intermittent hypoxia evokes persistent changes in extracellular striatal dopamine, locomotor activity and executive function, using a rodent model emulating apnea of prematurity in which rat pups are exposed to 20-second bursts of hypoxic gas mix containing 10% oxygen (60 events/h; 6 h/day) from postnatal days 7 to 11. To determine whether subtle repetitive hypoxic insults also induce expression of stress-related genes, we employed real-time RT-PCR to assay gene transcription in neonatal rats subjected to the same paradigm. In addition, we also measured expression of stress-induced transcripts in an age-matched cohort following a more severe oxidative stressor: permanent focal ischemia.

Cardiotrophin-1 protects cortical neuronal cells against free radical-induced injuries in vitro.

Cardiotrophin-1 (CT-1) was initially defined as a mediator of cardiomyocyte hypertrophy. Additional studies have showed that CT-1 enhanced survival of differentiated cardiac muscle cells and inhibited cardiac myocyte apoptosis after serum deprivation or cytokine stimulation. Moreover, CT-1 has recently been shown to act as a neuroregulatory cytokine in the peripheral nervous system.

Potential for protection and repair following injury to the developing brain: a role for erythropoietin?

Perinatal brain injury is a major contributor to perinatal morbidity and mortality, and a considerable number of these children will develop long term neurodevelopmental disabilities. Despite the severe clinical and socio-economic significance and the advances in neonatal care over the past twenty years, no therapy yet exists that effectively prevents or ameliorates detrimental neurodevelopmental effects in cases of perinatal/neonatal brain injury. Our objective is to review recent evidence in relation to the pervading hypothesis for targeting time-dependent molecular and cellular repair mechanisms in the developing brain.

Erythropoietin after focal cerebral ischemia activates the Janus kinase-signal transducer and activator of transcription signaling pathway and improves brain injury in postnatal day 7 rats.

Erythropoietin (Epo) plays a central role in erythropoiesis but also has neuroprotective properties. Recently, Epo-related neuroprotective studies used a hypoxic-ischemic neonatal model, which is different from focal stroke, a frequent cause of neonatal brain injury. We report on the effects of Epo treatment given after focal stroke and its potential neuroprotective mechanisms in postnatal day 7 rats with focal cerebral ischemia (FCI) achieved by occlusion of the middle cerebral artery.

A reproducible experimental model of focal cerebral ischemia in the neonatal rat.

Recent data suggest that the incidence of focal cerebral ischemia (FCI) and stroke is higher than previously recognized and could account for a large proportion of brain lesions in the preterm and full term neonate. Therefore, it is critically important to develop an appropriate model of FCI in neonatal animals. We describe here a modified model of permanent FCI in rat pups at postnatal day-7 (P7).

Permanent focal cerebral ischemia activates erythropoietin receptor in the neonatal rat brain.

Erythropoietin (Epo) has been shown to act as a neurotrophic and neuroprotective factor via binding to its receptor (EpoR) which is activated in adult brains following hypoxia and ischemia. However, no evidence suggests that cerebral ischemia can activate EpoR in the neonatal brain. In the present study, the changes in EpoR expression were investigated using a modified model of permanent focal cerebral ischemia (FCI) in 7-day-old rat pups.

Erythropoietin protects neurons against chemical hypoxia and cerebral ischemic injury by up-regulating Bcl-xL expression.

Erythropoietin (EPO) promotes neuronal survival after cerebral ischemia in vivo and after hypoxia in vitro. However, the mechanisms underlying the protective effects of EPO on ischemic/hypoxic neurons are not fully understood. The present in vitro experiments showed that EPO attenuated neuronal damage caused by chemical hypoxia at lower extracellular concentrations (10(- 4)-10(-2) U/ml) than were previously considered.