Cerebrovascular and Cerebrometabolic Effects of Intracarotid Infused Platelet-Activating Factor in Rats

Platelet-activating factor has been implicated in a variety of disease processes including ischemic brain injury and endotoxic shock, but its effects on cerebral blood flow (CBF) and metabolism in normal brain have not been described. The effects of platelet-activating factor on global CBF (hydrogen clearance) and the global cerebral metabolic rate for oxygen (CMRO2) were studied in halothane-N2O anesthetized Wistar rats. Hexadecyl-platelet-activating factor infused into the right carotid artery (67 pmol/min) for 60 min decreased mean arterial pressure (MAP) from 122 ±4 (x ± SEM) to 77 ± 6 mm Hg and CBF from 159 ± 12 to 116 ± 14 ml/100 g/min (p < 0.002). In contrast, CMRO2 increased from 9.7 ± 0.9 to 11.7 ± 1.1 ml/100 g/min after 15 min (p < 0.05). In controls rendered similarly hypotensive by blood withdrawal and infused with the platelet-activating factor vehicle, CMRO2 was unchanged, whereas CBF transiently decreased then returned to baseline at 60 min. These cerebrovascular and cerebrometabolic effects of PAF are reminiscent of and may be relevant to hypoperfusion and hypermetabolism observed after global brain ischemia and in endotoxic shock.

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Nanotherapeutic modulation of excitotoxicity and oxidative stress in acute brain injury

Nanobiomedicine ◽

10.1177/1849543520970819 ◽

2020 ◽

Vol 7 ◽

pp. 184954352097081

Author(s):

Rick Liao ◽

Thomas R Wood ◽

Elizabeth Nance

Keyword(s):

Oxidative Stress ◽

Brain Injury ◽

Calcium Influx ◽

Perinatal Asphyxia ◽

Pathological Process ◽

Global Brain Ischemia ◽

Excitatory Neurotransmitters ◽

Disease Site ◽

The Right ◽

Global Brain

Excitotoxicity is a primary pathological process that occurs during stroke, traumatic brain injury (TBI), and global brain ischemia such as perinatal asphyxia. Excitotoxicity is triggered by an overabundance of excitatory neurotransmitters within the synapse, causing a detrimental cascade of excessive sodium and calcium influx, generation of reactive oxygen species, mitochondrial damage, and ultimately cell death. There are multiple potential points of intervention to combat excitotoxicity and downstream oxidative stress, yet there are currently no therapeutics clinically approved for this specific purpose. For a therapeutic to be effective against excitotoxicity, the therapeutic must accumulate at the disease site at the appropriate concentration at the right time. Nanotechnology can provide benefits for therapeutic delivery, including overcoming physiological obstacles such as the blood–brain barrier, protect cargo from degradation, and provide controlled release of a drug. This review evaluates the use of nano-based therapeutics to combat excitotoxicity in stroke, TBI, and hypoxia–ischemia with an emphasis on mitigating oxidative stress, and consideration of the path forward toward clinical translation.

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Platelet-activating factor antagonist (ABT-491) decreases neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury

Brain Research ◽

10.1016/j.brainres.2007.01.094 ◽

2007 ◽

Vol 1143 ◽

pp. 193-198 ◽

Cited By ~ 21

Author(s):

Gulcin Bozlu ◽

Aytug Atici ◽

Ali Haydar Turhan ◽

Ayse Polat ◽

Ali Nayci ◽

...

Keyword(s):

Brain Injury ◽

Rat Model ◽

Neuronal Apoptosis ◽

Platelet Activating Factor ◽

Neonatal Rat ◽

Ischemic Brain Injury ◽

Ischemic Brain ◽

Hypoxic Ischemic Brain Injury ◽

Factor Antagonist ◽

Neonatal Rat Model

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Controlled reperfusion prevents neurologic injury after global brain ischemia in a novel ischemic brain model

Critical Care ◽

10.1186/cc7234 ◽

2009 ◽

Vol 13 (Suppl 1) ◽

pp. P70

Author(s):

Y Ko ◽

B Allen ◽

Z Tan ◽

S Sakhai ◽

G Buckberg

Keyword(s):

Brain Ischemia ◽

Neurologic Injury ◽

Global Brain Ischemia ◽

Ischemic Brain ◽

Global Brain ◽

Controlled Reperfusion

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Role of Astrocytic Mitochondria in Limiting Ischemic Brain Injury?

Physiology ◽

10.1152/physiol.00038.2017 ◽

2018 ◽

Vol 33 (2) ◽

pp. 99-112 ◽

Cited By ~ 3

Author(s):

Evelyn K. Shih ◽

Michael B. Robinson

Keyword(s):

Brain Injury ◽

Neuronal Activity ◽

Brain Function ◽

Functional Significance ◽

Normal Brain ◽

Ischemic Brain Injury ◽

Ischemic Brain ◽

Normal Brain Function

Until recently, astrocyte processes were thought to be too small to contain mitochondria. However, it is now clear that mitochondria are found throughout fine astrocyte processes and are mobile with neuronal activity resulting in positioning near synapses. In this review, we discuss evidence that astrocytic mitochondria confer selective resiliency to astrocytes during ischemic insults and the functional significance of these mitochondria for normal brain function.

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Platelet-Activating Factor Is an Important Mediator in Hypoxic Ischemic Brain Injury in the Newborn Rat

Neonatology ◽

10.1159/000014065 ◽

1998 ◽

Vol 74 (6) ◽

pp. 439-444 ◽

Cited By ~ 50

Author(s):

Mete Akisü ◽

Nilgün Kültürsay ◽

Isil Coker ◽

Afig Hüseyinov

Keyword(s):

Brain Injury ◽

Platelet Activating Factor ◽

Ischemic Brain Injury ◽

Newborn Rat ◽

Ischemic Brain ◽

Important Mediator ◽

Hypoxic Ischemic Brain Injury

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Functional, Perfusion and Diffusion MRI of acute Focal Ischemic Brain Injury

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9600132 ◽

2005 ◽

Vol 25 (10) ◽

pp. 1265-1279 ◽

Cited By ~ 85

Author(s):

Qiang Shen ◽

Hongxia Ren ◽

Haiying Cheng ◽

Marc Fisher ◽

Timothy Q Duong

Keyword(s):

Brain Injury ◽

Blood Oxygen Level Dependent ◽

Ischemic Brain Injury ◽

Blood Oxygen Level ◽

Ischemic Brain ◽

Disease States ◽

Somatosensory Cortices ◽

Fmri Response ◽

The Right ◽

And Diffusion

Combined functional, perfusion and diffusion magnetic resonance imaging (MRI) with a temporal resolution of 30 mins was performed on permanent and transient focal ischemic brain injury in rats during the acute phase. The apparent diffusion coefficient (ADC), baseline cerebral blood flow (CBF), and functional MRI (fMRI) blood-oxygen-level-dependent (BOLD), CBF, and CMRO2 responses associated with CO2 challenge and forepaw stimulation were measured. An automated cluster analysis of ADC and CBF data was used to track the spatial and temporal progression of different tissue types (e.g., normal, ‘at risk,’ and ischemic core) on a pixel-by-pixel basis. With permanent ischemia ( n = 11), forepaw stimulation fMRI response in the primary somatosensory cortices was lost, although vascular coupling (CO2 response) was intact in some animals. Control experiments in which the right common carotid artery was ligated without causing a stroke ( n = 8) showed that the delayed transit time had negligible effect on the fMRI responses in the primary somatosensory cortices. With temporary (15-mins, n = 8) ischemia, transient CBF and/or ADC declines were observed after reperfusion. However, no T2 or TTC lesions were observed at 24 h except in two animals, which showed very small subcortical lesions. Vascular coupling and forepaw fMRI response also remained intact. Finally, comparison of the relative and absolute fMRI signal changes suggest caution when interpreting percent changes in disease states in which the baseline signals are physiologically altered; quantitative CBF fMRI are more appropriate measures. This approach provides valuable information regarding ischemic tissue viability, vascular coupling, and functional integrity associated with ischemic injury and could have potential clinical applications.

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