Long-chain polyunsaturated fatty acids like conjugated linoleic acids (CLA) are required for normal neural development and cognitive function and have been ascribed various beneficial functions. Recently, oral CLA also has been shown to increase testosterone (T) biosynthesis, which is known to diminish traumatic brain injury (TBI)-induced neuropathology and reduce deficits induced by stroke in adult rats. To test the impact of CLA on cognitive recovery following a TBI, 5–6 month old male Sprague Dawley rats received a focal injury (craniectomy + controlled cortical impact (CCI; n = 17)) or Sham injury (craniectomy alone; n = 12) and were injected with 25 mg/kg body weight of Clarinol® G-80 (80% CLA in safflower oil; n = 16) or saline (n = 13) every 48 h for 4 weeks. Sham surgery decreased baseline plasma progesterone (P4) by 64.2% (from 9.5 ± 3.4 ng/mL to 3.4 ± 0.5 ng/mL; p = 0.068), T by 74.6% (from 5.9 ± 1.2 ng/mL to 1.5 ± 0.3 ng/mL; p < 0.05), 11-deoxycorticosterone (11-DOC) by 37.5% (from 289.3 ± 42.0 ng/mL to 180.7 ± 3.3 ng/mL), and corticosterone by 50.8% (from 195.1 ± 22.4 ng/mL to 95.9 ± 2.2 ng/mL), by post-surgery day 1. CCI injury induced similar declines in P4, T, 11-DOC and corticosterone (58.9%, 74.6%, 39.4% and 24.6%, respectively) by post-surgery day 1. These results suggest that both Sham surgery and CCI injury induce hypogonadism and hypoadrenalism in adult male rats. CLA treatment did not reverse hypogonadism in Sham (P4: 2.5 ± 1.0 ng/mL; T: 0.9 ± 0.2 ng/mL) or CCI-injured (P4: 2.2 ± 0.9 ng/mL; T: 1.0 ± 0.2 ng/mL, p > 0.05) animals by post-injury day 29, but rapidly reversed by post-injury day 1 the hypoadrenalism in Sham (11-DOC: 372.6 ± 36.6 ng/mL; corticosterone: 202.6 ± 15.6 ng/mL) and CCI-injured (11-DOC: 384.2 ± 101.3 ng/mL; corticosterone: 234.6 ± 43.8 ng/mL) animals. In Sham surgery animals, CLA did not alter body weight, but did markedly increase latency to find the hidden Morris Water Maze platform (40.3 ± 13.0 s) compared to saline treated Sham animals (8.8 ± 1.7 s). In CCI injured animals, CLA did not alter CCI-induced body weight loss, CCI-induced cystic infarct size, or deficits in rotarod performance. However, like Sham animals, CLA injections exacerbated the latency of CCI-injured rats to find the hidden MWM platform (66.8 ± 10.6 s) compared to CCI-injured rats treated with saline (30.7 ± 5.5 s, p < 0.05). These results indicate that chronic treatment of CLA at a dose of 25 mg/kg body weight in adult male rats over 1-month 1) does not reverse craniectomy- and craniectomy + CCI-induced hypogonadism, but does reverse craniectomy- and craniectomy + CCI-induced hypoadrenalism, 2) is detrimental to medium- and long-term spatial learning and memory in craniectomized uninjured rats, 3) limits cognitive recovery following a moderate-severe CCI injury, and 4) does not alter body weight.
Clarinol 1 G-80 (Lot 5385481001) was used in this study. There is an error in the description of Clarinol 1 G-80 in the fourth sentence of the first paragraph under the "CLA Administration" subheading in the Materials and Methods section. The description should be as follows: "Clarinol 1 G-80, is an oil mixture high in isomers of CLA (80%), comprised predominantly of c-9,t-11 (conjugated diene (CD)18:2) and t-10,c-12 (CD18:2) CLA (74.5%) with traces of oleic, palmitic and stearic acid (or safflower oil fatty acids)."A decimal error was made in the calculation of the dosage of Clarinol 1 intraperitoneally injected in the rats. A dose of 250mg/kg Clarinol 1 was delivered to the rats every other day (not 25 mg/kg every other day as stated in the article). This equates to~100 mg/kg of conjugated linoleic acid (CLA) per day and approximately two-fold the equivalent FDA recommended human dose (not half the FDA approved dose as stated in the article).There was an error in reporting the ages of the rats used in the study. Rats were assigned to the following groups: Sham + saline group (n = 5; 5-6 months of age), Sham + CLA group (n = 7; 5-6 months of age), controlled cortical impact (CCI) injury + saline group (n = 8; 15-16 months of age), CCI injury + CLA group (n = 9; 15-16 months of age). Since the incidence of traumatic brain injury increases in the elderly, aged rats were subjected to a CCI injury. The results indicate that Clarinol 1 at the dose injected intraperitoneally is detrimental to learning and memory in uninjured young adult rats, and limits cognitive recovery in aged rats following a CCI injury.The conclusions of the study focus on the effects of intraperitoneal CLA administration; conclusions cannot be drawn from the study data regarding the effects of oral administration of CLA, and discussion of the effects of dietary CLA in the article is speculative. The design of our experiment related to administration of CLA was motivated by the potential use of CLA in the treatment of TBI. Many individuals with TBI, particularly those with moderate to severe TBI cannot consume food, but can take treatments i.p., s.c. or i.v. Moreover, this experimental design allows us to know the exact amount delivered to each animal and avoid complications related to differences in consumption, or differences in intestinal uptake, of CLA by different animals. Potential differences in the effects of intermittent Clarinol 1 G-80 treatment (higher doses every other day), and between oral and intraperitoneal delivery, warrants further investigation.PLOS ONE | https://doi.org/10.1371/journal.pone.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Introduction Management of restless legs syndrome (RLS, aka Willis-Ekbom Disease) with dopaminergic agents is often complicated by development of augmentation. Clinical practice guidelines and stepwise algorithms suggest that prior to prescribing dopaminergic agents, clinicians should assess iron stores and consider alpha-2-delta agents (e.g. gabapentin). We developed an informatics approach to assess quality of care metrics for RLS management. Methods We used Veterans Affairs (VA) electronic health record data to identify a cohort of patients at a single tertiary care academic VA facility prescribed dopaminergic agents between 01 Jan 2018 to 31 Dec 2019. Patients with any prior codes for Parkinson’s disease were excluded. A random sample of charts were manually reviewed to determine if dopaminergic drugs were being prescribed for RLS or other indications. We then assessed for evidence of prior iron store assessments, iron repletion if appropriate, and alpha-2-delta agents (gabapentin, pregabalin). Results We identified 1160 patients treated with dopaminergic agents and no prior Parkinson’s codes. Chart reviews indicated 95% accuracy of this methodology to identify dopaminergic use for RLS. Evidence of pre-treatment iron storage assessment was missing in 30.2% for ferritin and 33.5% for transferrin saturation. Among those with iron studies present, lack of iron replacement was noted in 34% of those with ferritin <75 mcg/L and 33% of those with transferrin saturation <20%. Prior or concomitant prescriptions of alpha-2-delta agents was present in 59.7% of the cohort. Conclusion Our informatics approach provides an accurate and efficient means to quantify RLS care metrics. Results were most notable for a high proportion of dopaminergic-treated RLS patients without iron assessments and without iron repletion when stores were low. This methodology will inform future quality improvement initiatives to improve the delivery of guideline concordant RLS care. Support (If Any) This material is the result of work supported with resources and the use of facilities at the Minneapolis Veterans Affairs Health Care System, Minneapolis/USA.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.