Massive efflux of adenosine triphosphate into the extracellular space immediately after experimental traumatic brain injury

Moro,Nobuhiro; Ghavim,Sima S.; Sutton,Richard L.

doi:10.3892/etm.2021.10007

Massive efflux of adenosine triphosphate into the extracellular space immediately after experimental traumatic brain injury

Authors:
- Nobuhiro Moro
- Sima S. Ghavim
- Richard L. Sutton
View Affiliations

Affiliations: Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine, University of California, LA 90095‑6901, USA
Published online on: March 31, 2021 https://doi.org/10.3892/etm.2021.10007
Article Number: 575
Copyright: © Moro et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The aim of the current study was to determine effects of mild traumatic brain injury (TBI), with or without blockade of purinergic ATP Y1 (P2Y1) receptors or store‑operated calcium channels, on extracellular levels of ATP, glutamate, glucose and lactate. Concentrations of ATP, glutamate, glucose and lactate were measured in cerebral microdialysis samples obtained from the ipsilateral cortex and underlying hippocampus of rats with mild unilateral controlled cortical impact (CCI) or sham injury. Immediately after CCI, a large release of ATP was observed in the cortex (3.53‑fold increase of pre‑injury value) and hippocampus (2.97‑fold increase of pre‑injury value), with ATP returning to the baseline levels within 20 min post‑injury and remaining stable for during the 3‑h sampling period. In agreement with the results of previous studies, there was a significant increase in glutamate 20 min after CCI, which was concomitant with a decrease in extracellular glucose (20 min) and an increase in lactate (40‑60 min) in both brain regions after CCI. Addition of a selective P2Y1 receptor blocker (MRS2179 ammonium salt hydrate) to the microdialysis perfusate significantly lowered pre‑injury ATP and glutamate levels, and eliminated the post‑CCI peaks. Addition of a blocker of store‑operated calcium channels [2‑aminoethoxy diphenylborinate (2‑APB)] to the microdialysis perfusate significantly lowered pre‑injury ATP in the hippocampus, and attenuated the post‑CCI peak in both the cortex and hippocampus. 2‑APB treatment significantly increased baseline glutamate levels, but the values post‑injury did not differ from those in the sham group. Pre‑injury glucose levels, but not lactate levels, were increased by MRS2179 and decreased by 2‑APB. However, none of these treatments substantially altered the CCI‑induced reduction in glucose and increase in lactate in the cortex. In conclusion, the results of the present study demonstrated that a short although extensive release of ATP immediately after experimental TBI can be significantly attenuated by blockade of P2Y1 receptors or store‑operated calcium channels.

View Figures

View References

1	Bazargani N and Attwell D: Amines, astrocytes, and arousal. Neuron. 94:228–231. 2017.PubMed/NCBI View Article : Google Scholar
2	Harada K, Kamiya T and Tsuboi T: Gliotransmitter release from astrocytes: Functional, developmental, and pathological implications in the brain. Front Neurosci. 9(499)2015.PubMed/NCBI View Article : Google Scholar
3	De Pittà M, Brunel N and Volterra A: Astrocytes: Orchestrating synaptic plasticity? Neuroscience. 323:43–61. 2016.PubMed/NCBI View Article : Google Scholar
4	Lalo U, Bogdanov A and Pankratov Y: Age- and experience-related plasticity of ATP-mediated signaling in the neocortex. Front Cell Neurosci. 13(242)2019.PubMed/NCBI View Article : Google Scholar
5	Schwarz Y, Zhao N, Kirchhoff F and Bruns D: Astrocytes control synaptic strength by two distinct v-SNARE-dependent release pathways. Nat Neurosci. 20:1529–1539. 2017.PubMed/NCBI View Article : Google Scholar
6	Alberini CM, Cruz E, Descalzi G, Bessieres B and Gao V: Astrocyte glycogen and lactate: New insights into learning and memory mechanisms. Glia. 66:1244–1262. 2018.PubMed/NCBI View Article : Google Scholar
7	Henneberger C, Papouin T, Oliet SH and Rusakov DA: Long-term potentiation depends on release of D-serine from astrocytes. Nature. 463:232–236. 2010.PubMed/NCBI View Article : Google Scholar
8	Cai C, Zambach SA, Fordsmann JC, Lonstrup M, Thomsen KJ, Jensen AGK and Lauritzen M: In vivo three-dimensional two-photon microscopy to study conducted vascular responses by local ATP ejection using a glass micro-pipette. J Vis Exp. 148:2019.PubMed/NCBI View Article : Google Scholar
9	Haydon PG and Carmignoto G: Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev. 86:1009–1031. 2006.PubMed/NCBI View Article : Google Scholar
10	Takano T, Tian GF, Peng W, Lou N, Libionka W, Han X and Nedergaard M: Astrocyte-mediated control of cerebral blood flow. Nat Neurosci. 9:260–267. 2006.PubMed/NCBI View Article : Google Scholar
11	Corps KN, Roth TL and McGavern DB: Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol. 72:355–362. 2015.PubMed/NCBI View Article : Google Scholar
12	Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML and Gan WB: ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci. 8:752–758. 2005.PubMed/NCBI View Article : Google Scholar
13	Jassam YN, Izzy S, Whalen M, McGavern DB and El Khoury J: Neuroimmunology of traumatic brain injury: Time for a paradigm shift. Neuron. 95:1246–1265. 2017.PubMed/NCBI View Article : Google Scholar
14	Karve IP, Taylor JM and Crack PJ: The contribution of astrocytes and microglia to traumatic brain injury. Br J Pharmacol. 173:692–702. 2016.PubMed/NCBI View Article : Google Scholar
15	Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S and Inoue K: UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature. 446:1091–1095. 2007.PubMed/NCBI View Article : Google Scholar
16	Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB and Julius D: The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci. 9:1512–1519. 2006.PubMed/NCBI View Article : Google Scholar
17	Winkler U, Seim P, Enzbrenner Y, Köhler S, Sicker M and Hirrlinger J: Activity-dependent modulation of intracellular ATP in cultured cortical astrocytes. J Neurosci Res. 95:2172–2181. 2017.PubMed/NCBI View Article : Google Scholar
18	Melani A, Turchi D, Vannucchi MG, Cipriani S, Gianfriddo M and Pedata F: ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochem Int. 47:442–448. 2005.PubMed/NCBI View Article : Google Scholar
19	Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA and Nedergaard M: P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med. 10:821–827. 2004.PubMed/NCBI View Article : Google Scholar
20	Hinzman JM, Wilson JA, Mazzeo AT, Bullock MR and Hartings JA: Excitotoxicity and metabolic crisis are associated with spreading depolarizations in severe traumatic brain injury patients. J Neurotrauma. 33:1775–1783. 2016.PubMed/NCBI View Article : Google Scholar
21	Moro N, Ghavim SS, Harris NG, Hovda DA and Sutton RL: Pyruvate treatment attenuates cerebral metabolic depression and neuronal loss after experimental traumatic brain injury. Brain Res. 1642:270–277. 2016.PubMed/NCBI View Article : Google Scholar
22	Shijo K, Sutton RL, Ghavim SS, Harris NG and Bartnik-Olson BL: Metabolic fate of glucose in rats with traumatic brain injury and pyruvate or glucose treatments: A NMR spectroscopy study. Neurochem Int. 102:66–78. 2017.PubMed/NCBI View Article : Google Scholar
23	Taylor AN, Tio DL, Paydar A and Sutton RL: Sex differences in thermal, stress, and inflammatory responses to minocycline administration in rats with traumatic brain injury. J Neurotrauma. 35:630–638. 2018.PubMed/NCBI View Article : Google Scholar
24	Kawamura M, Gachet C, Inoue K and Kato F: Direct excitation of inhibitory interneurons by extracellular ATP mediated by P2Y1 receptors in the hippocampal slice. J Neurosci. 24:10835–10845. 2004.PubMed/NCBI View Article : Google Scholar
25	Bowser DN and Khakh BS: Vesicular ATP is the predominant cause of intercellular calcium waves in astrocytes. J Gen Physiol. 129:485–491. 2007.PubMed/NCBI View Article : Google Scholar
26	Heinke B and Sandkuhler J: Group I metabotropic glutamate receptor-induced Ca(2+)-gradients in rat superficial spinal dorsal horn neurons. Neuropharmacology. 52:1015–1023. 2007.PubMed/NCBI View Article : Google Scholar
27	Singaravelu K, Lohr C and Deitmer JW: Regulation of store-operated calcium entry by calcium-independent phospholipase A2 in rat cerebellar astrocytes. J Neurosci. 26:9579–9592. 2006.PubMed/NCBI View Article : Google Scholar
28	Fields RD: Nonsynaptic and nonvesicular ATP release from neurons and relevance to neuron-glia signaling. Semin Cell Dev Biol. 22:214–219. 2011.PubMed/NCBI View Article : Google Scholar
29	Illes P, Burnstock G and Tang Y: Astroglia-derived ATP modulates CNS neuronal circuits. Trends Neurosci. 42:885–898. 2019.PubMed/NCBI View Article : Google Scholar
30	Loiola EC and Ventura AL: Release of ATP from avian Müller glia cells in culture. Neurochem Int. 58:414–422. 2011.PubMed/NCBI View Article : Google Scholar
31	Muller MS and Taylor CW: ATP evokes Ca²⁺ signals in cultured foetal human cortical astrocytes entirely through G protein-coupled P2Y receptors. J Neurochem. 142:876–885. 2017.PubMed/NCBI View Article : Google Scholar
32	Molnar T, Dobolyi A, Nyitrai G, Barabas P, Heja L, Emri Z, Palkovits M and Kardos J: Calcium signals in the nucleus accumbens: Activation of astrocytes by ATP and succinate. BMC Neurosci. 12(96)2011.PubMed/NCBI View Article : Google Scholar
33	Svobodova I, Bhattaracharya A, Ivetic M, Bendova Z and Zemkova H: Circadian ATP release in organotypic cultures of the rat suprachiasmatic nucleus is dependent on P2X7 and P2Y receptors. Front Pharmacol. 9(192)2018.PubMed/NCBI View Article : Google Scholar
34	Guo H, Liu ZQ, Zhou H, Wang ZL, Tao YH and Tong Y: P2Y1 receptor antagonists mitigate oxygen and glucose deprivationinduced astrocyte injury. Mol Med Rep. 17:1819–1824. 2018.PubMed/NCBI View Article : Google Scholar
35	Koss DJ, Riedel G and Platt B: Intracellular Ca²⁺ stores modulate SOCCs and NMDA receptors via tyrosine kinases in rat hippocampal neurons. Cell Calcium. 46:39–48. 2009.PubMed/NCBI View Article : Google Scholar
36	Papanikolaou M, Lewis A and Butt AM: Store-operated calcium entry is essential for glial calcium signalling in CNS white matter. Brain Struct Funct. 222:2993–3005. 2017.PubMed/NCBI View Article : Google Scholar
37	Koizumi S, Fujishita K, Tsuda M, Shigemoto-Mogami Y and Inoue K: Dynamic inhibition of excitatory synaptic transmission by astrocyte-derived ATP in hippocampal cultures. Proc Natl Acad Sci USA. 100:11023–11028. 2003.PubMed/NCBI View Article : Google Scholar
38	Diniz C, Rodrigues M, Casarotto PC, Pereira VS, Crestani CC and Joca SRL: Monoamine involvement in the antidepressant-like effect induced by P2 blockade. Brain Res. 1676:19–27. 2017.PubMed/NCBI View Article : Google Scholar
39	Asadollahi M and Simani L: The diagnostic value of serum UCHL-1 and S100-B levels in differentiate epileptic seizures from psychogenic attacks. Brain Res. 1704:11–15. 2019.PubMed/NCBI View Article : Google Scholar
40	Lerchundi R, Huang N and Rose CR: Quantitative imaging of changes in astrocytic and neuronal adenosine triphosphate using two different variants of ATeam. Front Cell Neurosci. 14(80)2020.PubMed/NCBI View Article : Google Scholar
41	Burda JE, Bernstein AM and Sofroniew MV: Astrocyte roles in traumatic brain injury. Exp Neurol. 275:305–315. 2016.PubMed/NCBI View Article : Google Scholar
42	Wellmann M, Alvarez-Ferradas C, Maturana CJ, Saez JC and Bonansco C: Astroglial Ca²⁺-dependent hyperexcitability requires P2Y₁ purinergic receptors and pannexin-1 channel activation in a chronic model of epilepsy. Front Cell Neurosci. 12(446)2018.PubMed/NCBI View Article : Google Scholar
43	Sakuragi S, Niwa F, Oda Y, Mikoshiba K and Bannai H: Astroglial Ca²⁺ signaling is generated by the coordination of IP₃R and store-operated Ca²⁺ channels. Biochem Biophys Res Commun. 486:879–885. 2017.PubMed/NCBI View Article : Google Scholar
44	Li JH, Zhao ST, Wu CY, Cao X, Peng MR, Li SJ, Liu XA and Gao TM: Store-operated Ca²⁺ channels blockers inhibit lipopolysaccharide induced astrocyte activation. Neurochem Res. 38:2216–2226. 2013.PubMed/NCBI View Article : Google Scholar
45	Charles AC, Dirksen ER, Merrill JE and Sanderson MJ: Mechanisms of intercellular calcium signaling in glial cells studied with dantrolene and thapsigargin. Glia. 7:134–145. 1993.PubMed/NCBI View Article : Google Scholar
46	Obrenovitch TP and Urenjak J: Is high extracellular glutamate the key to excitotoxicity in traumatic brain injury? J Neurotrauma. 14:677–698. 1997.PubMed/NCBI View Article : Google Scholar
47	Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V and Volterra A: Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci. 10:331–339. 2007.PubMed/NCBI View Article : Google Scholar
48	Parri R and Crunelli V: Astrocytes target presynaptic NMDA receptors to give synapses a boost. Nat Neurosci. 10:271–273. 2007.PubMed/NCBI View Article : Google Scholar
49	Rose CR, Felix L, Zeug A, Dietrich D, Reiner A and Henneberger C: Astroglial glutamate signaling and uptake in the hippocampus. Front Mol Neurosci. 10(451)2017.PubMed/NCBI View Article : Google Scholar
50	Dorsett CR, McGuire JL, DePasquale EA, Gardner AE, Floyd CL and McCullumsmith RE: Glutamate neurotransmission in rodent models of traumatic brain injury. J Neurotrauma. 34:263–272. 2017.PubMed/NCBI View Article : Google Scholar
51	Gonzalez-Sanchez P, Del Arco A, Esteban JA and Satrustegui J: Store-operated calcium entry is required for mGluR-dependent long term depression in cortical neurons. Front Cell Neurosci. 11(363)2017.PubMed/NCBI View Article : Google Scholar
52	Carpenter KL, Jalloh I and Hutchinson PJ: Glycolysis and the significance of lactate in traumatic brain injury. Front Neurosci. 8(112)2015.PubMed/NCBI View Article : Google Scholar
53	Zeiler FA, Thelin EP, Helmy A, Czosnyka M, Hutchinson PJA and Menon DK: A systematic review of cerebral microdialysis and outcomes in TBI: Relationships to patient functional outcome, neurophysiologic measures, and tissue outcome. Acta Neurochir (Wien). 159:2245–2273. 2017.PubMed/NCBI View Article : Google Scholar
54	Jones DA, Ros J, Landolt H, Fillenz M and Boutelle MG: Dynamic changes in glucose and lactate in the cortex of the freely moving rat monitored using microdialysis. J Neurochem. 75:1703–1708. 2000.PubMed/NCBI View Article : Google Scholar
55	Clausen F, Hillered L and Gustafsson J: Cerebral glucose metabolism after traumatic brain injury in the rat studied by 13C-glucose and microdialysis. Acta Neurochir (Wien). 153:653–658. 2011.PubMed/NCBI View Article : Google Scholar
56	Prebil M, Chowdhury HH, Zorec R and Kreft M: Changes in cytosolic glucose level in ATP stimulated live astrocytes. Biochem Biophys Res Commun. 405:308–313. 2011.PubMed/NCBI View Article : Google Scholar
57	Tanaka M, Kawahara K, Kosugi T, Yamada T and Mioka T: Changes in the spontaneous calcium oscillations for the development of the preconditioning-induced ischemic tolerance in neuron/astrocyte co-culture. Neurochem Res. 32:988–1001. 2007.PubMed/NCBI View Article : Google Scholar
58	Xu Z, Xu W, Song Y, Zhang B, Li F and Liu Y: Blockade of store-operated calcium entry alleviates high glucose-induced neurotoxicity via inhibiting apoptosis in rat neurons. Chem Biol Interact. 254:63–72. 2016.PubMed/NCBI View Article : Google Scholar
59	Olianas MC, Dedoni S and Onali P: Involvement of store-operated Ca(2+) entry in activation of AMP-activated protein kinase and stimulation of glucose uptake by M3 muscarinic acetylcholine receptors in human neuroblastoma cells. Biochim Biophys Acta. 1843:3004–3017. 2014.PubMed/NCBI View Article : Google Scholar