scholarly journals Current Therapies for Neonatal Hypoxic–Ischaemic and Infection-Sensitised Hypoxic–Ischaemic Brain Damage

2021 ◽  
Vol 13 ◽  
Author(s):  
Konstantina Tetorou ◽  
Claudia Sisa ◽  
Arzo Iqbal ◽  
Kim Dhillon ◽  
Mariya Hristova
Keyword(s):  
Brain Damage ◽  
Animal Studies ◽  
Clinical Manifestations ◽  
Preterm Births ◽  
Mortality And Morbidity ◽  
Ischaemic Damage ◽  
Ischaemic Brain ◽  
Regional Vulnerability ◽  
Ischaemic Brain Damage ◽  
Experimental Treatments

Neonatal hypoxic–ischaemic brain damage is a leading cause of child mortality and morbidity, including cerebral palsy, epilepsy, and cognitive disabilities. The majority of neonatal hypoxic–ischaemic cases arise as a result of impaired cerebral perfusion to the foetus attributed to uterine, placental, or umbilical cord compromise prior to or during delivery. Bacterial infection is a factor contributing to the damage and is recorded in more than half of preterm births. Exposure to infection exacerbates neuronal hypoxic–ischaemic damage thus leading to a phenomenon called infection-sensitised hypoxic–ischaemic brain injury. Models of neonatal hypoxia–ischaemia (HI) have been developed in different animals. Both human and animal studies show that the developmental stage and the severity of the HI insult affect the selective regional vulnerability of the brain to damage, as well as the subsequent clinical manifestations. Therapeutic hypothermia (TH) is the only clinically approved treatment for neonatal HI. However, the number of HI infants needed to treat with TH for one to be saved from death or disability at age of 18–22 months, is approximately 6–7, which highlights the need for additional or alternative treatments to replace TH or increase its efficiency. In this review we discuss the mechanisms of HI injury to the immature brain and the new experimental treatments studied for neonatal HI and infection-sensitised neonatal HI.

scholarly journals Focal Cerebral Ischaemia in the Cat: Treatment with the Glutamate Antagonist MK-801 after Induction of Ischaemia

1988 ◽  
Vol 8 (5) ◽  
pp. 757-762 ◽  
Author(s):  
C. K. Park ◽  
D. G. Nehls ◽  
D. I. Graham ◽  
G. M. Teasdale ◽  
J. McCulloch
Keyword(s):  
Middle Cerebral Artery ◽  
Brain Damage ◽  
Cerebral Artery ◽  
Cerebral Ischaemia ◽  
Therapeutic Potential ◽  
Focal Cerebral Ischaemia ◽  
Mk 801 ◽  
Ischaemic Damage ◽  
Ischaemic Brain ◽  
Ischaemic Brain Damage

The effects of the glutamate N-methyl-D-aspartate receptor antagonist MK-801 in reducing ischaemic brain damage have been examined in anaesthetised cats, with drug treatment being initiated 2 h after the induction of cerebral ischaemia. Focal cerebral ischaemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischaemic damage was assessed at 16 predetermined stereotactic planes. Treatment with MK-801 (5 mg/kg, i.v.) 2 h after middle cerebral artery occlusion reduced significantly the volume of ischaemic damage (from 1,625 ± 384 mm3 of the cerebral hemisphere in vehicle-treated cats to 792 ± 385 mm3 in MK-801-treated cats). The demonstration of reduced ischaemic brain damage with MK-801, when the agent is administered after the induction of ischaemia, extends the therapeutic potential of such agents in the treatment of focal cerebral ischaemia in humans.

Spatiotemporal differences in vascular permeability after ischaemic brain damage

Neuroreport ◽  
2011 ◽  
Vol 22 (9) ◽  
pp. 424-427 ◽  
Author(s):  
Masato Yano ◽  
Naoyuki Kawao ◽  
Yukinori Tamura ◽  
Kiyotaka Okada ◽  
Shigeru Ueshima ◽  
...  
Keyword(s):  
Vascular Permeability ◽  
Brain Damage ◽  
Ischaemic Brain ◽  
Ischaemic Brain Damage

Ischaemic Brain Damage Induced by Rapid Lowering of Arterial Pressure in Hypertension

1984 ◽  
Vol 2 (3) ◽  
pp. 297???304 ◽  
Author(s):  
David I. Graham ◽  
Anne McGeorge ◽  
William Fitch ◽  
John V. Jones ◽  
Eric T. MacKenzie
Keyword(s):  
Arterial Pressure ◽  
Brain Damage ◽  
Ischaemic Brain ◽  
Ischaemic Brain Damage

NF-κB signalling in cerebral ischaemia

2006 ◽  
Vol 34 (6) ◽  
pp. 1291-1294 ◽  
Author(s):  
M. Schwaninger ◽  
I. Inta ◽  
O. Herrmann
Keyword(s):  
Infarct Size ◽  
Brain Damage ◽  
Cerebral Ischaemia ◽  
Neuronal Cell ◽  
Tissue Loss ◽  
Ischaemic Brain ◽  
Ischaemic Brain Damage ◽  
On The Road ◽  
Apoptosis And Inflammation

In acute stroke, neuronal apoptosis and inflammation are considered to be important mechanisms on the road to tissue loss and neurological deficit. Both apoptosis and inflammation depend on gene transcription. We have identified a signalling pathway that regulates transcription of genes involved in apoptosis and inflammation. In a mouse model of focal cerebral ischaemia, there is an induction of the cytokine TWEAK (tumour necrosis factor-like weak inducer of apoptosis) and its membrane receptor Fn14. TWEAK promotes neuronal cell death and activates the transcription factor NF-κB (nuclear factor κB) through the upstream kinase IKK [IκB (inhibitory κB) kinase]. In vivo, IKK is activated in neurons. Neuron-specific deletion of the subunit IKK2 or inhibition of IKK activity reduced the infarct size and neuronal cell loss. A pharmacological inhibitor of IKK also showed neuroprotective properties. IKK-dependent ischaemic brain damage is likely to be mediated by NF-κB, because neuron-specific inhibition of NF-κB through transgenic expression of the NF-κB superrepressor was found to reduce the infarct size. In summary, there is evidence that IKK/NF-κB signalling contributes to ischaemic brain damage and may provide suitable drug targets for the treatment of stroke.

scholarly journals Insights into cytoprotection from ground squirrel hibernation, a natural model of tolerance to profound brain oligaemia

2006 ◽  
Vol 34 (6) ◽  
pp. 1295-1298 ◽  
Author(s):  
Y.-J. Lee ◽  
J.M. Hallenbeck
Keyword(s):  
Signal Transduction ◽  
Blood Flow ◽  
Brain Damage ◽  
Oxygen Delivery ◽  
Ground Squirrel ◽  
Signal Transduction Pathways ◽  
Post Translational Modification ◽  
Ischaemic Brain ◽  
Ischaemic Brain Damage ◽  
Natural Tolerance

Progression of acute ischaemic brain damage is complex and multifactorial. Also, evidence suggests that participating molecules and signal transduction pathways can function differently in different cellular contexts. Hibernation torpor, a model of natural tolerance to profoundly reduced blood flow and oxygen delivery to brain, along with models of induced ischaemic tolerance can guide efforts to identify cytoprotective mechanisms that are multifactorial and that target multiple mechanisms in multiple cellular contexts. Post-translational modification of proteins by conjugation with the SUMO (small ubiquitin-related modifier) is massively increased in hibernation and may be such a mechanism.

scholarly journals ISCHAEMIC BRAIN DAMAGE: THE ROLE OF EXCITATORY ACTIVITY AND OF CALCIUM ENTRY

1985 ◽  
Vol 57 (1) ◽  
pp. 44-46 ◽  
Author(s):  
B. MELDRUM ◽  
M. EVANS ◽  
T. GRIFFITHS ◽  
R. SIMON
Keyword(s):  
Brain Damage ◽  
Calcium Entry ◽  
Ischaemic Brain ◽  
Excitatory Activity ◽  
Ischaemic Brain Damage
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