Raised intracranial pressure alters cortical vascular function and cephalic allodynia
Notice bibliographique
Résumé
Raised intracranial pressure (ICP) is associated with altered cerebral haemodynamics and cephalic pain. The relationship between the algetic response and cortical neurovascular changes in raised ICP is unclear. This study aimed to evaluate this relationship and determine whether lowering ICP (using a glucagon-like peptide-1 receptor agonist) could ameliorate the algetic response. We also sought to explore the role of calcitonin gene-related peptide in cephalic pain driven by raised ICP by inhibiting calcitonin gene-related peptide signalling and quantifying changes in the algetic response. In a rat model of raised ICP, created by intracisternal kaolin injection, mechanical thresholds were measured alongside steady-state potential and cerebral blood flow responses to spreading depolarization. Nuclear magnetic resonance spectroscopy evaluated energetic substrates in animals with raised ICP ex vivo. The glucagon-like peptide-1 receptor (GLP-1R) agonist exenatide and the calcitonin gene-related peptide receptor (CGRP-R) antagonist olcegepant were injected daily, and measurements were repeated. Kaolin increased ICP [median (range) 15.96 (8.97) mmHg, n = 8] versus controls [6.02 (1.79) mmHg, n = 6, P = 0.0007]. Animals with raised ICP exhibited reduced mechanical thresholds [mean (standard deviation) hind paw baseline: 5.78 (2.81) g, Day 7: 3.34 (2.22) g, P < 0.001; periorbital baseline: 6.13 (2.07) g, Day 7: 2.35 (1.91) g, n = 12, P < 0.001]. Depolarization and repolarization durations were increased [depolarization, raised ICP: 108.81 (222.12) s, n = 11, controls: 37.54 (108.38) s, n = 9, P = 0.038; repolarization, raised ICP: 1824.26 (3499.54) s, n = 12, controls: 86.96 (140.05) s, n = 9, P < 0.0001]. Cerebral blood flow change was also reduced [85.55 (30.84)%, n = 9] compared with controls [217.64 (37.70)%, n = 8, P < 0.0001]. Substrates for cellular energetics (ADP, ATP and NAD+) were depleted in rodent brains with raised ICP (P = 0.009, P = 0.018 and P = 0.011, respectively). Exenatide significantly lowered ICP [exenatide: 9.74 (6.09) mmHg, n = 19, vehicle: 18.27 (6.67) mmHg, n = 16, P = 0.004] and rescued changes in mechanical withdrawal. Exenatide recovered characteristic spreading depolarization responses [depolarization duration, exenatide: 56.46 (25.10) s, n = 7, vehicle: 115.98 (58.80) s, n = 6, P = 0.033; repolarization duration, exenatide: 177.55 (562.88) s, n = 7, vehicle: 800.85 (1988.67) s, n = 6, P = 0.002]. In the setting of raised ICP, olcegepant prevented changes in periorbital mechanical thresholds. We conclude that raised ICP disrupted the cortical neurovascular responses, reduced algetic thresholds and depleted crucial energetic substrates. Exenatide reduced ICP, improving algetic thresholds and cortical neurovascular changes. Importantly, olcegepant alleviated the cerebral algesia, suggesting a role for calcitonin gene-related peptide in driving pain responses in elevated ICP. These studies support the rationale that reducing ICP improves cephalic pain in conditions of raised ICP. Furthermore, the data suggest that headache pain in diseases associated with raised ICP could be ameliorated therapeutically though blockade of the calcitonin gene-related peptide pathway.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».