Pharmacological and genetic inhibition of NADPH oxidase does not reduce brain damage in different models of perinatal brain injury in newborn mice

Ischemia, especially pericontusional ischemia, is one of the leading causes of secondary brain damage after traumatic brain injury (TBI). So far efforts to improve cerebral blood flow (CBF) after TBI were not successful because of various reasons. We previously showed that nitric oxide (NO) applied by inhalation after experimental ischemic stroke is transported to the brain and induces vasodilatation in hypoxic brain regions, thus improving regional ischemia, thereby improving brain damage and neurological outcome. As regional ischemia in the traumatic penumbra is a key mechanism determining secondary posttraumatic brain damage, the aim of the current study was to evaluate the effect of NO inhalation after experimental TBI. NO inhalation significantly improved CBF and reduced intracranial pressure after TBI in male C57 Bl/6 mice. Long-term application (24 hours NO inhalation) resulted in reduced lesion volume, reduced brain edema formation and less blood–brain barrier disruption, as well as improved neurological function. No adverse effects, e.g., on cerebral auto-regulation, systemic blood pressure, or oxidative damage were observed. NO inhalation might therefore be a safe and effective treatment option for TBI patients.

Download Full-text

Cerebral acid-base and gas metabolism in brain injury

Journal of Neurosurgery ◽

10.3171/jns.1970.33.5.0498 ◽

1970 ◽

Vol 33 (5) ◽

pp. 498-505 ◽

Cited By ~ 55

Author(s):

R. Zupping

Keyword(s):

Metabolic Acidosis ◽

Brain Injury ◽

Brain Damage ◽

Close Correlation ◽

Respiratory Alkalosis ◽

Acid Base ◽

Content Type ◽

Arterial Blood ◽

Gas Metabolism ◽

Permanent Brain Damage

✓ Acid-base and gas parameters of CSF, jugular venous and arterial blood were measured in 45 patients with brain injury in the first 12 days after trauma or operation. CSF metabolic acidosis together with respiratory alkalosis and hypoxemia in the cerebral venous and arterial blood were the most characteristic findings. A close correlation between the severity of brain damage and the intensity of the CSF metabolic acidosis and arterial hypocapnia was revealed. It was concluded that brain hypoxia and acidosis play an important role in the development of cerebral edema and permanent brain damage.

Download Full-text

Novel Synthetic and Natural Therapies for Traumatic Brain Injury

Current Neuropharmacology ◽

10.2174/1570159x19666210225145957 ◽

2021 ◽

Vol 19 ◽

Author(s):

Denise Battaglini ◽

Dorota Siwicka-Gieroba ◽

Patricia RM Rocco ◽

Fernanda Ferreira Cruz ◽

Pedro Leme Silva ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Brain Damage ◽

Molecular Mechanisms ◽

Antioxidant Properties ◽

Secondary Brain Injury ◽

Specific Recommendation ◽

Novel Therapies ◽

Secondary Brain Damage ◽

Late Treatment

: Traumatic brain injury (TBI) is a major cause of disability and death worldwide. The initial mechanical insult results in tissue and vascular disruption with hemorrhages and cellular necrosis that is followed by a dynamic secondary brain damage that presumably results in additional destruction of the brain. In order to minimize deleterious consequences of the secondary brain damage-such as inflammation, bleeding or reduced oxygen supply. The old concept of the -staircase approach- has been updated in recent years by most guidelines and should be followed as it is considered the only validated approach for the treatment of TBI. Besides, a variety of novel therapies have been proposed as neuroprotectants. The molecular mechanisms of each drug involved in inhibition of secondary brain injury can result as potential target for the early and late treatment of TBI. However, no specific recommendation is available on their use in clinical setting. The administration of both synthetic and natural compounds, which act on specific pathways involved in the destructive processes after TBI, even if usually employed for the treatment of other diseases, can show potential benefits. This review represents a massive effort towards current and novel therapies for TBI that have been investigated in both pre-clinical and clinical settings. This review aims to summarize the advancement in therapeutic strategies basing on specific and distinct -target of therapies-: brain edema, ICP control, neuronal activity and plasticity, anti-inflammatory and immunomodulatory effects, cerebral autoregulation, antioxidant properties, and future perspectives with the adoption of mesenchymal stromal cells.

Download Full-text

Abstract TP406: Ipsilesional Myelination is Impaired in Children With Perinatal Arterial Stroke

Stroke ◽

10.1161/str.48.suppl_1.tp406 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Sabrina Yu ◽

Helen Carlson ◽

Adam Kirton

Keyword(s):

Brain Injury ◽

Neurological Disorders ◽

Repeated Measures ◽

Population Based ◽

T Test ◽

Biological Processes ◽

Typically Developing ◽

Inclusion Criteria ◽

Perinatal Brain Injury ◽

Perinatal Stroke

Introduction: Stroke is a leading cause of perinatal brain injury and cerebral palsy. Current therapeutic efforts focus on optimizing developmental curves but the biological processes dictating these outcomes are poorly understood. Alterations in myelination are recognized as a major determinant of outcome in preterm brain injury but are unexplored in perinatal stroke (PS). Hypothesis: Ipsilesional delays in myelination occur in children with PS and are associated with poor developmental outcome. Methods: Participants were identified through the Alberta Perinatal Stroke Project, a population-based research cohort. Inclusion criteria were: 1) MRI-confirmed, unilateral arterial PS, 2) T1-weighted MRI >6mo, 3) absence of other neurological disorders, 4) neurological outcome (Pediatric Stroke Outcome Measure, PSOM), and 5) motor assessments (Assisting Hand Assessment, AHA; Melbourne Assessment). FreeSurfer software measured hemispheric asymmetry in myelination intensity. A second method using ImageJ validated the detection of myelination asymmetry. Overall PSOM scores were classified as poor (>1) or not. Repeated measures ANOVA compared perilesional, ipsilesional remote, and contralesional homologous regions. Myelination ratios for stroke cases were compared to typically developing controls (t-test), PSOM scores (t-test), and motor assessments (Pearson’s correlation). Results: Nineteen arterial stroke cases (mean age: 13.73±4.0yo) and 27 controls (mean age: 12.52±3.7yo) were studied. Stroke cases showed a greater degree of asymmetry with lower myelination in the lesioned hemisphere, compared to controls (p<0.001). Myelination in perilesional regions was decreased compared to ipsilesional remote (p<0.001) and contralesional homologous areas (p<0.001). Ipsilesional remote regions were decreased compared to homologous regions on the contralesional hemisphere (p=0.009). Contralesional myelination was also less than controls (p<0.001). Myelination ratios were not associated with PSOM, AHA, or Melbourne scores (p=0.144, 0.218, 0.366 respectively). Conclusion: Myelination of uninjured brain in the lesioned hemisphere is altered in children with PS. Further study is required to determine clinical significance.

Download Full-text