Neuroprotective effect of indomethacin in normal perfusion pressure breakthrough phenomenon

Abstract Loss of cerebral autoregulation in normal perfusion pressure breakthrough (NPPB) phenomenon has been reported in other Central Nervous System diseases such as neonatal intraventricular haemorrhage. Several studies have demonstrated that low-dose indomethacin prevents this latter condition. A previous rat model was used to resemble NPPB phenomenon. Study animals were distributed in 4 groups that received 3 doses of indomethacin at different concentrations prior to fistula occlusion 60 days after its creation. Control animals received saline solution. Intracranial pressure (ICP) increased in all groups following fistula creation, whereas mean arterial pressure (MAP) and cerebral perfusion pressure (CPP) decreased as a manifestation of cerebral hypoperfusion and intracranial hypertension. The administration of indomethacin was associated with raised MAP and CPP, as well as decreased ICP. Sodium fluorescein extravasation was slight in study animals when comparing with control ones. Histological analysis evidenced diffuse ischaemic changes with signs of neuronal apoptosis in all brain layers in control animals. These findings were only focal and slight in study animals. The results suggest the usefulness of indomethacin to revert, at least partially, the haemodynamic effects of NPPB phenomenon in this experimental model, as well as to reduce BBB disruption and histological ischemia observed in absence of indomethacin.

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Experimental rat model of chronic cerebral hypoperfusion–reperfusion mimicking normal perfusion pressure breakthrough phenomenon

Neurocirugía ◽

10.1016/j.neucir.2019.11.002 ◽

2020 ◽

Vol 31 (5) ◽

pp. 209-215

Author(s):

Juan Manuel Revuelta ◽

Álvaro Zamarrón ◽

José Fortes ◽

Gregorio Rodríguez-Boto ◽

Jesús Vaquero ◽

...

Keyword(s):

Rat Model ◽

Perfusion Pressure ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Experimental Rat Model ◽

Normal Perfusion Pressure Breakthrough

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Normal perfusion pressure breakthrough: the role of capillaries

Journal of Neurosurgery ◽

10.3171/jns.1997.86.3.0519 ◽

1997 ◽

Vol 86 (3) ◽

pp. 519-524 ◽

Cited By ~ 63

Author(s):

Lali H. S. Sekhon ◽

Michael K. Morgan ◽

Ian Spence

Keyword(s):

Brain Tissue ◽

Perfusion Pressure ◽

Brain Parenchyma ◽

Cerebral Hypoperfusion ◽

Cell Region ◽

Complete Excision ◽

Content Type ◽

Normal Perfusion Pressure Breakthrough ◽

Fine Print ◽

Adjacent Brain

✓ Excision of human cerebral arteriovenous malformations (AVMs) can be complicated by postoperative edema and hemorrhage in adjacent brain tissue, despite the complete excision of the malformation. Various theories have purported to explain the hemodynamic basis for this predisposition, including disordered autoregulation causing “normal perfusion pressure breakthrough” and obstruction of venous drainage leading to “occlusive hyperemia.” This study did not evaluate the arterial or venous circulations in this scenario, but rather examined the capillaries in adjacent brain parenchyma for any structural deficiencies that would predispose the brain to the postoperative formation of edema and hemorrhage. Arteriovenous fistulas (AVFs) were created surgically in the necks of 10 male Sprague—Dawley rats, which caused chronic cerebral hypoperfusion with a reduction in cerebral blood flow of between 25% and 50%. Ten age-matched animals were used as controls. Twenty-six weeks after AVF formation the animals were killed and perfusion fixed. Their brain tissue was prepared for light microscopic studies by staining for glial fibrillary acidic protein or for transmission electron microscopy. In the CA1 pyramidal cell region of the hippocampus, it was found that in the animals with AVFs there was increased capillary density and absent astrocytic foot processes in some of these vessels. It was concluded that these vessels had developed as a result of neovascularization in response to chronic cerebral ischemia and that their anatomical configuration made them prone to mechanical weakness and instability following the increase in perfusion pressure that occurs in adjacent brain parenchyma after AVM excision. The authors believe that this study pinpoints a structural accompaniment to the hemodynamic changes that occur in brain tissue in the vicinity of cerebral AVMs that predispose these areas to the formation of edema and hemorrhage after AVM excision.

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Experimental rat model of chronic cerebral hypoperfusion–reperfusion mimicking normal perfusion pressure breakthrough phenomenon

Neurocirugía (English Edition) ◽

10.1016/j.neucie.2019.11.001 ◽

2020 ◽

Vol 31 (5) ◽

pp. 209-215

Author(s):

Juan Manuel Revuelta ◽

Álvaro Zamarrón ◽

José Fortes ◽

Gregorio Rodríguez-Boto ◽

Jesús Vaquero ◽

...

Keyword(s):

Rat Model ◽

Perfusion Pressure ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Experimental Rat Model ◽

Normal Perfusion Pressure Breakthrough

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Ginkgolide B promotes oligodendrocyte precursor cell differentiation and survival via Akt/CREB/bcl-2 signaling pathway after white matter lesion

Experimental Biology and Medicine ◽

10.1177/1535370221989955 ◽

2021 ◽

pp. 153537022198995

Author(s):

Jian Huang ◽

Jun Yang ◽

Xingju Zou ◽

Shilun Zuo ◽

Jing Wang ◽

...

Keyword(s):

White Matter ◽

White Matter Lesion ◽

Neuroprotective Effect ◽

Precursor Cell ◽

Cerebral Hypoperfusion ◽

Ginkgolide B ◽

Oligodendrocyte Precursor Cell ◽

Learning Abilities ◽

Phosphorylated Akt ◽

Oligodendrocyte Precursor

White matter lesion (WML) is caused by chronic cerebral hypoperfusion, which are usually associated with cognitive impairment. Evidence from recent studies has shown that ginkgolide B has a neuroprotective effect that could be beneficial for the treatment of ischemia; however, it is not clear whether ginkgolide B has a protective effect on WML. Our data show that ginkgolide B can promote the differentiation of oligodendrocyte precursor cell (OPC) into oligodendrocytes and promote oligodendrocyte survival following a WML. Ginkgolide B (5, 10, 20 mg/kg) or saline is administered intraperitoneally every day after WML. After 4 weeks, the data of Morris water maze suggested that rats’ memory and learning abilities were impaired, and the administration of ginkgolide B enhanced behavioral achievement. Also, treatment with ginkgolide B significantly attenuated this loss of myelin. Our result suggests that ginkgolide B promotes the differentiation of OPC into oligodendrocytes. We also found that ginkgolide B ameliorates oligodendrocytes apoptosis. Furthermore, ginkgolide B enhanced the expression of phosphorylated Akt and CREB. In conclusion, our data firstly show that ginkgolide B promotes oligodendrocyte genesis and oligodendrocyte myelin following a WML, possibly involving the Akt and CREB pathways.

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Neuroprotective effect of Na + /H + exchangers isoform‐1 inactivation against 6‐hydroxydopamine‐induced mitochondrial dysfunction and neuronal apoptosis in Parkinson's disease models

Drug Development Research ◽

10.1002/ddr.21799 ◽

2021 ◽

Author(s):

Ruixian Xing ◽

Xuewen Liu ◽

Buxian Tian ◽

Yan Cheng ◽

Longguang Li

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mitochondrial Dysfunction ◽

Neuronal Apoptosis ◽

Neuroprotective Effect ◽

Disease Models ◽

6 Hydroxydopamine

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A new rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations

Journal of Neurosurgery ◽

10.3171/jns.2002.97.5.1198 ◽

2002 ◽

Vol 97 (5) ◽

pp. 1198-1202 ◽

Cited By ~ 35

Author(s):

Jian Hai ◽

Meixiu Ding ◽

Zhilin Guo ◽

Bingyu Wang

Keyword(s):

Electron Microscopy ◽

Animal Model ◽

Arteriovenous Malformations ◽

Perfusion Pressure ◽

Chronic Cerebral Hypoperfusion ◽

Cerebral Hypoperfusion ◽

Model Group ◽

Content Type ◽

The Right ◽

Fine Print

Object. A new experimental model of chronic cerebral hypoperfusion was developed to study the effects of systemic arterial shunting and obstruction of the primary vessel that drains intracranial venous blood on cerebral perfusion pressure (CPP), as well as cerebral pathological changes during restoration of normal perfusion pressure. Methods. Twenty-four Sprague—Dawley rats were randomly assigned to either a sham-operated group, an arteriovenous fistula (AVF) group, or a model group (eight rats each). The animal model was readied by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein (EJV) and the ispilateral common carotid artery (CCA), followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Systemic mean arterial pressure (MAP), draining vein pressure (DVP), and CPP were monitored and compared among the three groups preoperatively, immediately postoperatively, and again 90 days later. Following occlusion of the fistula after a 90-day interval, blood—brain barrier (BBB) disruption and water content in the right cortical tissues of the middle cerebral artery territory were confirmed and also quantified with transmission electron microscopy. Formation of a fistula resulted in significant decreases in MAP and CPP, and a significant increase in DVP in the AVF and model groups. Ninety days later, there were still significant increases in DVP and decreases in CPP in the model group compared with the other groups (p < 0.05). Damage to the BBB and brain edema were noted in animals in the model group during restoration of normal perfusion pressure by occlusion of the fistula. Electron microscopy studies revealed cerebral vasogenic edema and/or hemorrhage in various amounts, which correlated with absent astrocytic foot processes surrounding some cerebral capillaries. Conclusions. The results demonstrated that an end-to-side anastomosis between the distal EJV and CCA can induce a decrease in CPP, whereas a further chronic state of cerebral hypoperfusion may be caused by venous outflow restriction, which is associated with perfusion pressure breakthrough. This animal model conforms to the basic hemodynamic characteristics of human cerebral arteriovenous malformations.

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The use of intraarterial papaverine in the management of vasospasm complicating arteriovenous malformation resection

Journal of Neurosurgery ◽

10.3171/jns.1995.82.2.0296 ◽

1995 ◽

Vol 82 (2) ◽

pp. 296-299 ◽

Cited By ~ 20

Author(s):

Michael K. Morgan ◽

Maurice J. Day ◽

Nicholas Little ◽

Verity Grinnell ◽

William Sorby

Keyword(s):

Arteriovenous Malformation ◽

Perfusion Pressure ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Venous Occlusion ◽

Neurological Deterioration ◽

Unusual Complication ◽

Content Type ◽

First Case ◽

Normal Perfusion Pressure Breakthrough ◽

Fine Print

✓ The authors report two cases of treatment by intraarterial papaverine of cerebral vasospasm complicating the resection of an arteriovenous malformation (AVM). Both cases had successful reversal of vasospasm documented on angiography. In the first case sustained neurological improvement occurred, resulting in a normal outcome by the time of discharge. In the second case, neurological deterioration occurred with the development of cerebral edema. This complication was thought to be due to normal perfusion pressure breakthrough, on the basis of angiographic arterial vasodilation and increased cerebral blood flow. These two cases illustrate an unusual complication of surgery for AVMs and demonstrate that vasospasm (along with intracranial hemorrhage, venous occlusion, and normal perfusion pressure breakthrough) should be considered in the differential diagnosis of delayed neurological deterioration following resection of these lesions. Although intraarterial papaverine may be successful in dilating spastic arteries, it may also result in pathologically high flows following AVM resection. However, this complication has not been seen in our experience of treating aneurysmal subarachnoid hemorrhage by this technique.

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Effects of chronic cerebral hypoperfusion and low-dose progesterone treatment on apoptotic processes, expression and subcellular localization of key elements within Akt and Erk signaling pathways in rat hippocampus

Neuroscience ◽

10.1016/j.neuroscience.2015.10.040 ◽

2015 ◽

Vol 311 ◽

pp. 308-321 ◽

Cited By ~ 7

Author(s):

M. Stanojlović ◽

I. Guševac ◽

I. Grković ◽

J. Zlatković ◽

N. Mitrović ◽

...

Keyword(s):

Subcellular Localization ◽

Signaling Pathways ◽

Low Dose ◽

Chronic Cerebral Hypoperfusion ◽

Rat Hippocampus ◽

Cerebral Hypoperfusion ◽

Erk Signaling ◽

Progesterone Treatment

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the Comparred Effect of Zyprasidone and Haloperidol at Hippocampal and Frontal Cortex at Rats

European Psychiatry ◽

10.1016/s0924-9338(09)71393-8 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

D. Marinescu ◽

L. Mogoanta ◽

T. Udristoiu

Keyword(s):

Adverse Event ◽

Frontal Cortex ◽

Negative Symptoms ◽

Structural Changes ◽

Saline Solution ◽

Neuroprotective Effect ◽

Neuronal Loss ◽

D2 Receptors ◽

Cerebral Structure ◽

The Brain

Background:The alteration of hippocampal and prefrontal structures is linked with schizophrenia cognitive impairment and negative symptoms. the antipsychotics can induced apoptotic mechanisms correlated with the psychopharmacological mechanism of excesive blocking of the D2 receptors. Distress determined increase of the glucocorticoid aggression wich drive to the decrease of neuroprotective capacity at the brain level.Methods:We formed 5 study lots (5 adults rats) and a control lot. the substancies were administrated intraperitoneal, daily, saline solution equivalent to: ziprasidone (1.25mg/kg/day) and haloperidole (0.20mg/kg/day), dexametasone (0.20mg/kg/day):N1 - Haloperidole; N2 - Dexametasone; N3 - Ziprasidone; N4 - Dexametasone and Haloperidole; N5 - Dexametasone and Ziprasidone; N6 -control lot.We monitorised the cardiovascular function, respiration and EPS, without signaling any serious deadly adverse event. the rats were sacrificed during the 10th day and 21th day.Results:Frontal cortex and hippocamp were the most intensely affected even since the 10-th day to the N4 (haloperidole and dexametasone) lot with massive neuronal loss at the VI, V, and IV frontal cerebral layers.The lots treated with ziprasidone presented significant lesser structural changes in frontal cortex and hippocamp, comparative to haloperidole. the lots treated with dexametasone and ziprasidone (N5) are lesser affected at the cerebral structure level.Conclusions:Haloperidole has a significant decrease in neuroprotection. Ziprasidone demonstrated an neuroprotective effect.

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