Protective effects of fluoxetine on decompression sickness in mice
Jean-Eric Blatteau, Sandrine Barre, Aurelie Pascual, Olivier Castagna, Jacques H Abraini, Jean-Jacques Risso, Nicolas Vallee, Jean-Eric Blatteau, Sandrine Barre, Aurelie Pascual, Olivier Castagna, Jacques H Abraini, Jean-Jacques Risso, Nicolas Vallee
Abstract
Massive bubble formation after diving can lead to decompression sickness (DCS) that can result in central nervous system disorders or even death. Bubbles alter the vascular endothelium and activate blood cells and inflammatory pathways, leading to a systemic pathophysiological process that promotes ischemic damage. Fluoxetine, a well-known antidepressant, is recognized as having anti-inflammatory properties at the systemic level, as well as in the setting of cerebral ischemia. We report a beneficial clinical effect associated with fluoxetine in experimental DCS. 91 mice were subjected to a simulated dive at 90 msw for 45 min before rapid decompression. The experimental group received 50 mg/kg of fluoxetine 18 hours before hyperbaric exposure (n = 46) while controls were not treated (n = 45). Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine IL-6 detection. There were significantly fewer manifestations of DCS in the fluoxetine group than in the controls (43.5% versus 75.5%, respectively; p = 0.004). Survivors showed a better and significant neurological recovery with fluoxetine. Platelets and red cells were significantly decreased after decompression in controls but not in the treated mice. Fluoxetine reduced circulating IL-6, a relevant marker of systemic inflammation in DCS. We concluded that fluoxetine decreased the incidence of DCS and improved motor recovery, by limiting inflammation processes.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
![Figure 1. Flow chart describing the experimental…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3493517/bin/pone.0049069.g001.jpg)
![Figure 2. Percents of symptomatic mice suffering…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3493517/bin/pone.0049069.g002.jpg)
Figure 3. Percents of successful grip tests…
Figure 3. Percents of successful grip tests (suspension time ≥30 sec) in dark grey for…
Figure 4. Percents of blood cells consumption…
Figure 4. Percents of blood cells consumption after decompression from the baseline in dark grey…
- DCS or DCI? The difference and why it matters.Mitchell SJ. Mitchell SJ. Diving Hyperb Med. 2019 Sep 30;49(3):152-153. doi: 10.28920/dhm49.3.152-153. Diving Hyperb Med. 2019. PMID: 31523788 Free PMC article.
- Fluoxetine stimulates anti-inflammatory IL-10 cytokine production and attenuates sensory deficits in a rat model of decompression sickness.Blatteau JE, de Maistre S, Lambrechts K, Abraini J, Risso JJ, Vallée N. Blatteau JE, et al. J Appl Physiol (1985). 2015 Dec 15;119(12):1393-9. doi: 10.1152/japplphysiol.00602.2015. Epub 2015 Oct 22. J Appl Physiol (1985). 2015. PMID: 26494447
- Hyperbaric Physics.Jones MW, Brett K, Han N, Wyatt HA. Jones MW, et al. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 28846268 Free Books & Documents.
- Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness.Pontier JM, Vallée N, Ignatescu M, Bourdon L. Pontier JM, et al. J Appl Physiol (1985). 2011 Mar;110(3):724-9. doi: 10.1152/japplphysiol.00230.2010. Epub 2011 Jan 6. J Appl Physiol (1985). 2011. PMID: 21212250 Free PMC article.
- Clopidogrel reduces the inflammatory response of lung in a rat model of decompression sickness.Bao XC, Chen H, Fang YQ, Yuan HR, You P, Ma J, Wang FF. Bao XC, et al. Respir Physiol Neurobiol. 2015 Jun;211:9-16. doi: 10.1016/j.resp.2015.02.003. Epub 2015 Mar 14. Respir Physiol Neurobiol. 2015. PMID: 25784626
-
- Bert P (1978) Barometric pressure (La Pression Barométrique, 1878). Bethesda, MD: Undersea Medical Society; translated by Hitchcok, MA and Hitchcok, FA in 1978. 1183 p.
-
- Francis T, Mitchell S (2003) Pathophysiology of decompression sickness. Brubbak A, Neuman T (eds): The Bennett and Elliot’s physiology and medicine of diving (5th Ed). London: WB Saunders. pp 530–556.
-
- Blatteau JE, Gempp E, Simon O, Coulange M, Delafosse B, et al. (2011) Prognostic factors of spinal cord decompression sickness in recreational diving: retrospective and multicentric analysis of 279 cases. Neurocrit Care 15: 120–127. - PubMed
-
- Ersson A, Linder C, Ohlsson K, Ekholm A (1998) Cytokine response after acute hyperbaric exposure in the rat. Undersea Hyperb Med 25: 217–221. - PubMed
-
- Broussolle B, Méliet JL (2006) Broussolle B (2e Ed) Physiologie et médecine de la plongée. Paris: Ellipses, Editions Marketing. 880 p.
- Animals
- Decompression Sickness* / drug therapy
- Decompression Sickness* / pathology
- Diving / physiology
- Embolism, Air* / drug therapy
- Embolism, Air* / pathology
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / pathology
- Fluoxetine / administration & dosage*
- Humans
- Mice
- Platelet Count
- Protective Agents / administration & dosage
- Protective Agents
- Fluoxetine
- Full Text Sources
- Medical
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![Figure 3. Percents of successful grip tests…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3493517/bin/pone.0049069.g003.jpg)
Figure 4. Percents of blood cells consumption…
Figure 4. Percents of blood cells consumption after decompression from the baseline in dark grey…
- DCS or DCI? The difference and why it matters.Mitchell SJ. Mitchell SJ. Diving Hyperb Med. 2019 Sep 30;49(3):152-153. doi: 10.28920/dhm49.3.152-153. Diving Hyperb Med. 2019. PMID: 31523788 Free PMC article.
- Fluoxetine stimulates anti-inflammatory IL-10 cytokine production and attenuates sensory deficits in a rat model of decompression sickness.Blatteau JE, de Maistre S, Lambrechts K, Abraini J, Risso JJ, Vallée N. Blatteau JE, et al. J Appl Physiol (1985). 2015 Dec 15;119(12):1393-9. doi: 10.1152/japplphysiol.00602.2015. Epub 2015 Oct 22. J Appl Physiol (1985). 2015. PMID: 26494447
- Hyperbaric Physics.Jones MW, Brett K, Han N, Wyatt HA. Jones MW, et al. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. 2022 Sep 26. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 28846268 Free Books & Documents.
- Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness.Pontier JM, Vallée N, Ignatescu M, Bourdon L. Pontier JM, et al. J Appl Physiol (1985). 2011 Mar;110(3):724-9. doi: 10.1152/japplphysiol.00230.2010. Epub 2011 Jan 6. J Appl Physiol (1985). 2011. PMID: 21212250 Free PMC article.
- Clopidogrel reduces the inflammatory response of lung in a rat model of decompression sickness.Bao XC, Chen H, Fang YQ, Yuan HR, You P, Ma J, Wang FF. Bao XC, et al. Respir Physiol Neurobiol. 2015 Jun;211:9-16. doi: 10.1016/j.resp.2015.02.003. Epub 2015 Mar 14. Respir Physiol Neurobiol. 2015. PMID: 25784626
-
- Bert P (1978) Barometric pressure (La Pression Barométrique, 1878). Bethesda, MD: Undersea Medical Society; translated by Hitchcok, MA and Hitchcok, FA in 1978. 1183 p.
-
- Francis T, Mitchell S (2003) Pathophysiology of decompression sickness. Brubbak A, Neuman T (eds): The Bennett and Elliot’s physiology and medicine of diving (5th Ed). London: WB Saunders. pp 530–556.
-
- Blatteau JE, Gempp E, Simon O, Coulange M, Delafosse B, et al. (2011) Prognostic factors of spinal cord decompression sickness in recreational diving: retrospective and multicentric analysis of 279 cases. Neurocrit Care 15: 120–127. - PubMed
-
- Ersson A, Linder C, Ohlsson K, Ekholm A (1998) Cytokine response after acute hyperbaric exposure in the rat. Undersea Hyperb Med 25: 217–221. - PubMed
-
- Broussolle B, Méliet JL (2006) Broussolle B (2e Ed) Physiologie et médecine de la plongée. Paris: Ellipses, Editions Marketing. 880 p.
- Animals
- Decompression Sickness* / drug therapy
- Decompression Sickness* / pathology
- Diving / physiology
- Embolism, Air* / drug therapy
- Embolism, Air* / pathology
- Endothelium, Vascular / drug effects
- Endothelium, Vascular / pathology
- Fluoxetine / administration & dosage*
- Humans
- Mice
- Platelet Count
- Protective Agents / administration & dosage
- Protective Agents
- Fluoxetine
- Full Text Sources
- Medical
![Figure 4. Percents of blood cells consumption…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3493517/bin/pone.0049069.g004.jpg)
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Source: PubMed