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Basal MAP and HR recover in spinal cord injured rats grafted with BS-NSCs. In a representative cohort (n = 3/group), telemetry recording indicates significantly lower basal MAP and higher HR in rats with SCI and no treatment 10 weeks after injury (*p < 0.05). In contrast, both cardiovascular parameters recover to the level of naïve rats 8 weeks after BS-NSC grafting (10 weeks post-injury) (both p > 0.05; ANOVA followed by Fisher's post hoc).
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High thoracic or cervical spinal cord injury (SCI) can lead to cardiovascular dysfunction. To monitor cardiovascular parameters, we implanted a catheter connected to a radio transmitter into the femoral artery of rats that underwent a T4 spinal cord transection with or without grafting of embryonic brainstem-derived neural stem cells expressing gre...
Context in source publication
Context 1
... animals with SCI alone, MAP was significantly reduced whereas HR increased compared to naïve animals, consistent with previous reports 9 . In animals with BS-NSC grafting, MAP and HR approached levels measured in naïve animals (Figure 2). During colorectal distension, a rat was regarded as dysreflexic if the noxious stimulation produced a rise in MAP and a decrease in HR 3,8 . ...
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Introduction
Autonomic dysreflexia (AD) affects about 70% of individuals with spinal cord injury (SCI) and can have severe consequences, including death if not promptly detected and managed. The current gold standard for AD detection involves continuous blood pressure monitoring, which can be inconvenient. Therefore, a non-invasive detection device...
Citations
... Physiological signals over extended periods of time can be recorded in unstressed animals (i.e., unhindered by anesthesia or restraint). This approach has now been used to study cardiovascular function in rats (Hou et al., 2014), renal tissue oxygen tension (Koeners et al., 2016), and intracranial pressure (Guild et al., 2015). ...
Intramedullary pressure increases after spinal cord injury, and this can be an important factor for secondary spinal cord injury. Until now there have been no studies of the dynamic changes of intramedullary pressure after spinal cord injury. In this study, telemetry systems were used to observe changes in intramedullary pressure in the 72 hours following spinal cord injury to explore its pathological mechanisms. Spinal cord injury was induced using an aneurysm clip at T10 of the spinal cord of 30 Japanese white rabbits, while another 32 animals were only subjected to laminectomy. The feasibility of this measurement was assessed. Intramedullary pressure was monitored in anesthetized and conscious animals. The dynamic changes of intramedullary pressure after spinal cord injury were divided into three stages: stage I (steep rise) 1–7 hours, stage II (steady rise) 8–38 hours, and stage III (descending) 39–72 hours. Blood-spinal barrier permeability, edema, hemorrhage, and histological results in the 72 hours following spinal cord injury were evaluated according to intramedullary pressure changes. We found that spinal cord hemorrhage was most severe at 1 hour post-spinal cord injury and then gradually decreased; albumin and aquaporin 4 immunoreactivities first increased and then decreased, peaking at 38 hours. These results confirm that severe bleeding in spinal cord tissue is the main cause of the sharp increase in intramedullary pressure in early spinal cord injury. Spinal cord edema and blood-spinal barrier destruction are important factors influencing intramedullary pressure in stages II and III of spinal cord injury.
... Physiological signals over extended periods of time can be recorded in unstressed animals (i.e., unhindered by anesthesia or restraint). This approach has now been used to study cardiovascular function in rats (Hou et al., 2014), renal tissue oxygen tension (Koeners et al., 2016), and intracranial pressure (Guild et al., 2015). ...
Exploring the relationship between different structure of the spinal cord and functional assessment after spinal cord injury is important. Quantitative diffusion tensor imaging can provide information about the microstructure of nerve tissue and can quantify the pathological damage of spinal cord white matter and gray matter. In this study, a custom-designed spinal cord contusion-impactor was used to damage the T10 spinal cord of beagles. Diffusion tensor imaging was used to observe changes in the whole spinal cord, white matter, and gray matter, and the Texas Spinal Cord Injury Score was used to assess changes in neurological function at 3 hours, 24 hours, 6 weeks, and 12 weeks after injury. With time, fractional anisotropy values after spinal cord injury showed a downward trend, and the apparent diffusion coefficient, mean diffusivity, and radial diffusivity first decreased and then increased. The apparent diffusion-coefficient value was highly associated with the Texas Spinal Cord Injury Score for the whole spinal cord (R = 0.919, P = 0.027), white matter (R = 0.932, P = 0.021), and gray matter (R = 0.882, P = 0.048). Additionally, the other parameters had almost no correlation with the score (P > 0.05). In conclusion, the highest and most significant correlation between diffusion parameters and neurological function was the apparent diffusion-coefficient value for white matter, indicating that it could be used to predict the recovery of neurological function accurately after spinal cord injury.
Preeclampsia (PE), a hypertensive pregnancy disorder, can originate from varied etiology. Placenta malperfusion has long been considered the primary cause of PE. However, we and others have showed that this disorder can also result from heightened inflammation at the maternal-fetal interface. To advance our understanding of this understudied PE subtype, it is important to establish validated rodent models to study the pathophysiology and test therapies. We evaluated three previously described approaches to induce inflammation-mediated PE-like features in pregnant rats: 1) Tumor necrosis factor-α (TNF-α) infusion via osmotic pump from gestational day (GD) 14-19 at 50ng/day/animal; 2) Polyinosinic:polycytidylic acid (Poly I:C) intraperitoneal (IP) injections from GD 10-18 (alternate days) at 10mg/kg/day/animal; and, 3) Lipopolysaccharide (LPS) IP injections from GD 13-18 at 20ug-70ug/kg/day per animal. Maternal blood pressure was measured by tail-cuff. Upon sacrifice, fetal and placenta weights were recorded. Placenta histomorphology was assessed using H&E sections. Placenta inflammation was determined by quantifying TNF-α levels and inflammatory gene expression. Placenta metabolic and mitochondrial health were determined by measuring mitochondrial respiration rates and placenta NAD⁺/NADH content. Of the three rodent models tested, we found that Poly I:C and LPS decreased both fetal weight and survival; and correlated with a reduction in region specific placenta growth. As the least effective model characterized, TNF-α treatment resulted in a subtle decrease in fetal/placenta weight and placenta mitochondrial respiration. Only the LPS model was able to induce maternal hypertension and exhibited pronounced placenta metabolic and mitochondrial dysfunction, common features of PE. Thus, the rat LPS model was most effective for recapitulating features observed in cases of human inflammatory PE. Future mechanistic and/or therapeutic intervention studies focuses on this distinct PE patient population may benefit from the employment of this rodent model of PE.
Study design:
Preclinical pharmacology.
Objectives:
To determine whether blocking substance P signaling attenuates the hypertension and bradycardia evoked by colorectal distension (CRD) in spinal cord injured (SCI) rats.
Setting:
University laboratory in Pennsylvania, U.S.A.
Methods:
Tachykinin NK1 receptor antagonists were administered 30 min prior to CRD three weeks after complete spinal cord transection at the 4th thoracic (T4) level. The dose range, route of administration, and pretreatment time was based on published data demonstrating occupancy of brain NK1 receptors in rodents.
Results:
Subcutaneous (SC) administration of 10-30 mg/kg GR205171 ((2S,3S)-N-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine dihydrochloride) reduced CRD-induced hypertension and bradycardia by 55 and 49%, respectively, compared with pretreatment values. There was no effect of GR205171 on resting blood pressure or heart rate. In contrast, the same dose range of CP-99,994 ((2S,3S)-N-[(2-methoxyphenyl)methyl]-2-phenyl-3-piperidinamine dihydrochloride) had no effect on CRD-induced cardiovascular responses.
Conclusions:
The effective dose range of GR205171 to alleviate autonomic dysreflexia is consistent with the blockade of NK1 receptors on pelvic sensory afferents in the lumbosacral spinal cord, which may in turn prevent the over-excitation of sympathetic preganglionic neurons (SPNs) that regulate blood pressure and heart rate. The findings provide preclinical support for the utility of NK1 receptor antagonists to treat autonomic dysreflexia in people with SCI. The difference in the effects of the two NK1 receptor antagonists may reflect the ~200-fold lower affinity of CP-99,994 than GR205171 for the rat NK1 receptor.
Objective:
This study aimed to investigate the effects of radio-telemetry implantation surgery on blood pressure (BP) and renin-angiotensin-aldosterone system (RAAS), calcitonin gene-related peptide (CGRP) and endothelin-1 (ET-1) in rats.
Methods:
Six spontaneously hypertensive rat (SHRs) and six WKY rats successfully implanted telemetry were used as experimental group, while six SHRs and six Wistar-Kyoto (WKY) rats of comparable age, weight and BP free from implantation surgery were used as normal control group. BP in each group was monitored using the tail cuff method; furthermore, the content of PRA-I, PRA-II, ALD and ET-1, CGRP in plasma was measured with the ELISA.
Results:
After implantation surgery, there was no general strain difference in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in either SHRs or WKY rats. But there was a significant increase in renin and a suppression of the difference in angiotensin and aldosterone in SHRs and WKY rats. CGRP, ET-1 showed an overall decrease in SHRs and WKY rats.
Conclusion:
These results indicated that although radio-telemetry is regarded as an efficient and reliable technology for measuring BP, we must pay attention to the influence of the operation itself on BP regulators. After the implantation surgery, decrease in arterial BP or decrease in circulating blood volume might stimulate the secretion of renin, and with the increase of BP and local blood flow, the level of CGRP was decreased. And the decrease of ET-1 may be a kind of protective suppression.
