Homolateral cerebrocortical changes in neuropeptide and receptor expression after minimal cortical infarction

Bree, Laurence Van; Zhang, F.; Schiffmann, Serge N.; Halleux, P; Mailleux, Pierre; Vanderhaeghen, Jean‐Jacques

doi:10.1016/0306-4522(95)00277-p

Cited by 10 publications

(6 citation statements)

References 61 publications

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“…Previously, a higher expression of SP has been found in ischemic cerebral tissue in animal models [ 10 , 11 , 12 ] and in four infants with brain-stem infarction [ 13 ]. In addition, higher serum levels of SP levels have been found in 18 cerebral ischemia patients compared with healthy controls [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, SP could play a role in ischemic stroke: there are data suggesting that SP is involved in neurogenic inflammation, classical inflammation, and thrombosis [ 2 , 3 ]. Animal models of cerebral ischemia have shown a higher expression of SP in ischemic cerebral tissue [ 10 , 11 , 12 ]. However, SP has been scarcely explored in ischemic stroke patients [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

Lorente

Martı́n

Almeida

et al. 2016

IJMS

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Substance P (SP), a member of tachykinin family, is involved in the inflammation of the central nervous system and in the appearance of cerebral edema. Higher serum levels of SP have been found in 18 patients with cerebral ischemia compared with healthy controls. The aim of our multi-center study was to analyze the possible association between serum levels of SP and mortality in ischemic stroke patients. We included patients with malignant middle cerebral artery infarction (MMCAI) and a Glasgow Coma Scale (GCS) lower than 9. Non-surviving patients at 30 days (n = 31) had higher serum concentrations of SP levels at diagnosis of severe MMCAI than survivors (n = 30) (p < 0.001). We found in multiple regression an association between serum concentrations of SP higher than 362 pg/mL and mortality at 30 days (Odds Ratio = 5.33; 95% confidence interval = 1.541–18.470; p = 0.008) after controlling for age and GCS. Thus, the major novel finding of our study was the association between serum levels of SP and mortality in patients suffering from severe acute ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

Lorente

Martı́n

Almeida

et al. 2016

IJMS

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“…Although speculative, such a mechanism would serve to restrict the extent of the NO-mediated relaxation and could become particularly important in situations where an increase in blood flow could have detrimental effects. The recent findings of marked increases in NPY immunoreactivity and mRNA expression in the peri-ischemic zone or following cortical infarction in rats (Cheung and Chechetto, 1995;Van Bree et al, 1995) point to a need for a better understanding of the role(s) of NPY in the physiology and pathophysiology of the cerebral microcirculation. The preferential association of perivascular NPY terminals with intracortical capillaries-including the associated astrocytes, although not excluding a vasomotor role (Owman et al, 1978)-could also suggest alternate functions for these pericapillary NPY terminals.…”

Section: Functional Implicationsmentioning

confidence: 97%

Associations between neuropeptide Y nerve terminals and intraparenchymal microvessels in rat and human cerebral cortex

Abounader

Hamel

1997

J. Comp. Neurol.

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Neuropeptide Y (NPY) can influence local brain perfusion, possibly via direct relationships with the microvascular bed. To evaluate this possibility, the authors quantitatively analyzed by light and electron microscopy the morphological associations between immunostained NPY neuronal elements and intraparenchymal microvessels in the rat and human cerebral cortex. At the light microscopic level in the rat frontoparietal cortex, about 16% of NPY neurons and large proximal processes as well as a subset of nerve terminals not affected by double sympathectomy were associated with penetrating arterioles and local microvessels. In human temporal cortex, a dense network of NPY nerve fibers was observed, many of which approached and/or contacted intracortical vessels. At the ultrastructural level, 14% of NPY axonal varicosities in the rat cerebral cortex were considered perivascular and associated with capillaries (approximately 70%) or microarterioles (approximately 30%). They were particularly enriched in the immediate vicinity (< 0.25 micron) of the microvessels, where the perivascular astrocytic leaflets represented a frequent target. In human cerebral cortex, NPY varicosities were observed in proximity to microvessels corresponding primarily to capillaries. Perivascular NPY varicosities never established synaptic junctions with vascular or astroglial elements. The results show that central NPY nerve terminals associate with microvessels and perivascular astroglial cells in the rat and human cerebral cortex. Thus, NPY released from these nerves could possibly influence (via a parasynaptic mode of action) vascular and/or astrocytic functions depending on the distribution of NPY receptors in these cellular compartments. These results provide morphological support for the effects of NPY on brain perfusion and homeostasis.

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“…Notably, this experimental condition imitates situations at which BK, NT and SP are available concurrently and may potentiate each other's biological effects. Elevated levels of all three peptides were reported in experimental models of ischaemic stroke 45‐48 and traumatic brain injury, 49‐51 as well as in patients suffering these conditions 13,52 . Severity and subsequent mortality associated with ischaemic stroke and traumatic brain injury have been linked to the elevated levels of BK, NT and SP in these studies.…”

Section: Discussionmentioning

confidence: 70%

“…To evaluate selectivity of BK, NT and SP effects on BBB permeability, in a separate set of experiments, we used small molecule antagonists of B1, B2, NT1 and NK1 receptors to block the respective F I G U R E 7 Human recombinant neurolysin has a negligible effect on barrier function. CTR90F and CTR65M brain microvascular endothelial cells were treated with different concentrations of recombinant neurolysin (rNln) (0.1-1 µg mL -1 ) followed by transendothelial electrical resistance (TEER) (A) and fluorescein permeability (B) measurements (n = 6-13 for no rNln, ie, '0' group and 3-4 for all other groups; **P < 0.01 compared to no rNln group) Elevated levels of all three peptides were reported in experimental models of ischaemic stroke [45][46][47][48] and traumatic brain injury, [49][50][51] as well as in patients suffering these conditions. 13,52 Severity and effects of these agents in ischaemic stroke and/or traumatic brain injury models.…”

Section: Discussionmentioning

confidence: 99%

Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model

Al‐Ahmad

Pervaiz

Karamyan

2021

J Neuroendocrinology

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Increased brain microvascular permeability and disruption of blood-brain barrier (BBB) function are among hallmarks of several acute neurodegenerative disorders, including stroke. Numerous studies suggest the involvement of bradykinin (BK), neurotensin (NT) and substance P (SP) in BBB impairment and oedema formation after stroke; however, there is paucity of data in regard to the direct effects of these peptides on the brain microvascular endothelial cells (BMECs) and BBB. The present study aimed to evaluate the direct effects of BK, NT and SP on the permeability of BBB in an in vitro model based on human induced pluripotent stem cell (iPSC)derived BMECs. Our data indicate that all three peptides increase BBB permeability in a concentration-dependent manner in an in vitro model formed from two different iPSC lines (CTR90F and CTR65M) and widely used hCMEC/D3 human BMECs. The combination of BK, NT and SP at a sub-effective concentration also resulted in increased BBB permeability in the iPSC-derived model indicating potentiation of their action. Furthermore, we observed abrogation of BK, NT and SP effects with pretreatment of pharmacological blockers targeting their specific receptors. Additional mechanistic studies indicate that the short-term effects of these peptides are not mediated through alteration of tight-junction proteins claudin-5 and occludin, but likely involve redistribution of F-actin and secretion of vascular endothelial growth factor. This is the first experimental study to document the increased permeability of the BBB in response to direct action of NT in an in vitro model. In addition, our study confirms the expected but not well-documented, direct effect of SP on BBB permeability and adds to the well-recognised actions of BK on BBB. Lastly, we demonstrate that peptidase neurolysin can neutralise the effects of these peptides on BBB, suggesting potential therapeutic implications.

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Homolateral cerebrocortical changes in neuropeptide and receptor expression after minimal cortical infarction

Cited by 10 publications

References 61 publications

Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

Serum Levels of Substance P and Mortality in Patients with a Severe Acute Ischemic Stroke

Associations between neuropeptide Y nerve terminals and intraparenchymal microvessels in rat and human cerebral cortex

Neurolysin substrates bradykinin, neurotensin and substance P enhance brain microvascular permeability in a human in vitro model

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