Related Experiment Video
Updated: Jul 21, 2026
07:54
Detecting Behavioral Deficits in Rats After Traumatic Brain Injury
Published on: January 30, 2018
18.1K
Sex-Specific and Dose-Dependent Effects of Drag-Reducing Polymers on Microcirculation and Tissue Oxygenation in Rats
Denis E Bragin1,2, Olga A Bragina3, Marina V Kameneva4
1Lovelace Biomedical Research Institute, Albuquerque, NM, USA. dbragin@lovelacebiomedical.org.
Advances in Experimental Medicine and Biology
|October 16, 2023
Summary
Drag-reducing polymers (DRP) improve blood flow and oxygen delivery to the brain after traumatic brain injury (TBI). DRP treatment enhanced microvascular cerebral blood flow (mvCBF) and protected the blood-brain barrier (BBB) in a dose-dependent manner.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Physiology
Background:
- Traumatic brain injury (TBI) impairs cerebral blood flow and oxygen delivery, leading to ischemia and reduced metabolic rate.
- Previous studies demonstrated drag-reducing polymers (DRP) improve hemodynamics in TBI models.
- The effects of DRP on microvascular cerebral blood flow (mvCBF) and tissue oxygenation post-TBI require further investigation, including dose-dependency and sex-specific responses.
Purpose of the Study:
- To evaluate the sex-specific and dose-dependent effects of DRP on mvCBF and tissue oxygenation in a rat model of moderate TBI.
- To assess DRP's impact on blood-brain barrier (BBB) permeability and intracranial pressure following TBI.
- To determine the optimal DRP dosage for mitigating TBI-induced cerebrovascular dysfunction.
Main Methods:
- In vivo two-photon laser scanning microscopy was used to monitor microvascular perfusion, tissue oxygenation, and BBB permeability in the rat parietal cortex.
- Moderate TBI was induced via lateral fluid-percussion (1.5 ATA, 100 ms) followed by 4 hours of monitoring.
- DRP was administered intravenously at doses of 1, 2, or 4 ppm within 30 minutes post-TBI. Statistical analysis involved two-way ANOVA and Mann-Whitney U tests.
Main Results:
- Moderate TBI progressively decreased mvCBF, induced tissue hypoxia, and caused BBB degradation in the pericontusion zone.
- DRP administration dose-dependently increased near-wall flow velocity and arteriolar flow rate, enhancing capillary perfusion and tissue oxygenation.
- DRP treatment protected the BBB, mitigated TBI-induced increases in intracranial pressure, and reduced microcirculatory shunting and capillary stagnation, with 4 ppm DRP being most effective.
Conclusions:
- Intravenous DRP effectively improves microvascular perfusion and tissue oxygenation following moderate TBI in rats.
- DRP treatment demonstrates a dose-dependent protective effect on the blood-brain barrier and mitigates cerebrovascular dysfunction post-TBI.
- While no significant sex differences were observed, DRP at 4 ppm showed a trend towards better outcomes, particularly in female rats.
Related Concept Videos
01:24Drug Toxicity: Risk factors
Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
01:24Drug Toxicity: Dose-Dependent Reactions
Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
01:23Toxicity Testing in Animals
Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...