Laboratory studyIncreased xanthine oxidase activity after traumatic brain injury in rats
Introduction
Both direct mechanical injury (primary injury) and secondary autodestructive reactions (secondary injury) participate in the pathogenesis of tissue damage after traumatic brain injury (TBI). In recent years, much of our attention has been focused on secondary injury in TBI, an important potential target for therapeutic intervention.
It has been suggested that one of the most important factors precipitating secondary brain injury after TBI, and which leads to ischemia and cerebral edema, is oxygen free radical (OFR)-induced lipid peroxidation.[1], [2], [3], [4], [5], [6] OFR such as superoxide, hydrogen peroxide, and hydroxyl are highly reactive molecules implicated in the pathology of TBI through a mechanism known as oxidative stress.
Several mechanisms of OFR production have been proposed after TBI, including calcium activation of phospholipases, nitric oxide (NO) synthase, xanthine oxidase (XO), the Fenton and Haber–Weiss reactions and via the actions of inflammatory cells.[7], [8] An understanding of the mechanisms of OFR production may lead to novel therapies to reduce or prevent secondary injury after TBI. Therefore, we investigated the time-dependent changes in XO activity, one of the major sources of OFR in the cell cytoplasm, in the rat brain after TBI.
Section snippets
Materials and methods
The local Institutional Animal Care committee approved all protocols used in this study. Male Sprague-Dawley rats (n = 35), weighing 170–200 g, were allocated randomly into the following 5 groups, with 7 rats in each group.
- (A)
Control: craniotomy without brain injury, non-traumatized brain samples obtained immediately.
- (B)
Sham: craniotomy without brain injury, non-traumatized brain samples obtained 24 h later.
- (C)
Trauma 2 h: craniotomy and TBI, brain samples obtained 2 h post-trauma.
- (D)
Trauma 8 h: craniotomy and
Results
There was a statistically significant difference in the mean XO enzyme activity among the groups (p < 0.05). There was no significant difference between the control and sham groups (p > 0.05). Although there was a significant difference between the control and all trauma groups (p < 0.05), there was no statistically significant difference between each trauma group (p > 0.05). TBI increased brain XO enzyme activity at 2 h post-surgery but XO activity did not then change over 24 h (Fig. 1).
There was a
Discussion
The primary insult results in a cascade of neurotoxic events after TBI, which includes lipid peroxidation. Numerous experimental studies have reported that TBI results in an increase in OFR.[11], [12] There are a number of potential sources and mechanisms for OFR production and lipid peroxidation after TBI.
It has been shown that TBI results in increased extracellular concentrations of glutamate.[13], [14] The activation of glutamate receptors results in increase in free calcium levels in the
References (27)
- et al.
Central nervous system trauma and stroke: II. Physiological and pharmacological evidence for the involvement of oxygen radicals and lipid peroxidation
Free Radic Biol Med
(1989) - et al.
Central nervous system trauma and stroke: I. Biochemical considerations for oxygen radical formation and lipid peroxidation
Free Radic Biol Med
(1989) - et al.
Determination of malonaldehyde precursor in tissues by thiobarbituric acid test
Anal Biochem
(1978) - et al.
The chemistry of DNA damage from nitric oxide and peroxynitrite
Mutat Res
(1999) - et al.
Oxygen radicals and the nervous system
Trends Neurosci
(1985) - et al.
The reduction of cytochrome C by milk xanthine oxidase
J Biol Chem
(1968) - et al.
Allopurinol inhibits uric acid accumulation in the rat brain following focal cerebral ischemia
Brain Res
(1989) - et al.
Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases
Neurosci Lett
(1997) - et al.
Oxygen radicals in brain injury
Cent Nerv Syst Trauma
(1986) - et al.
Superoxide production in experimental brain injury
J Neurosurg
(1986)
Inhibition by free radical scavengers and by cyclooxygenase inhibitors of pial arteriolar abnormalities from concussive brain injury in cats
Circ Res
Reactive oxygen species and the central nervous system
J Neurochem
Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling
J Neurochem
Cited by (41)
Allopurinol attenuates repeated traumatic brain injury in old rats: A preliminary report
2022, Experimental NeurologyCitation Excerpt :Oxidative stress is reported to play a key role in secondary injury and to cause neurotoxicity including inflammation, cell damage, and neuronal death through a series of reactions (Juurlink and Paterson, 1998; Tyurin et al., 2000). Studies showed that Xanthine oxidase (XO) enzyme activity may increase within 2 h after TBI during oxidative stress and may play an important role in the generation of reactive oxygen species (ROS) (Battelli et al., 1996; Hewinson et al., 2004; Solaroglu et al., 2005). XO catalyzes the conversion of hypoxanthine to xanthine and of xanthine to uric acid and reduces oxygen into ROS (Isik et al., 2006), the excess of which is detrimental to neuronal cells.
A preliminary model of football-related neural stress that integrates metabolomics with transcriptomics and virtual reality
2022, iScienceCitation Excerpt :More research is required to elucidate the role of phosphate in the full TBI spectrum. Lastly, all xanthine metabolites increased at Post suggesting either (a) an increase in caffeine consumption (Bonati et al., 1982), (b) activation of xanthine oxidases (Solaroglu et al., 2005), or (c) a combination of both (Signoretti et al., 2010). Caffeine has various anti-inflammatory and neuroprotective effects in both animals and humans, especially in relation to neurodegenerative disease and TBI (Kolahdouzan and Hamadeh, 2017).
Oxidized phospholipid signaling in traumatic brain injury
2018, Free Radical Biology and MedicineWhat are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients?
2016, International ImmunopharmacologyCitation Excerpt :Lipid peroxidation induced by oxidative damage is a phenomenon that induces alterations in cellular membranes. The highest level of MDA is detected thirty minutes after brain trauma which is maintained elevated 72 h after the injury onset [26,59,60]. In the present study, an increase in MDA level was maintained in control group during six days of the evaluation.