Naikui Liu

Bio: Naikui Liu is an academic researcher from University of Louisville. The author has contributed to research in topics: Spinal cord & Spinal cord injury. The author has an hindex of 7, co-authored 7 publications receiving 378 citations.

A novel role of phospholipase A2 in mediating spinal cord secondary injury.

Abstract: Objective To investigate whether phospholipase A2 (PLA2) plays a role in the pathogenesis of spinal cord injury (SCI). Methods Biochemical, Western blot, histological, immunohistochemical, electron microscopic, electrophysiological, and behavior assessments were performed to investigate (1) SCI-induced PLA2 activity, expression, and cellular localization after a contusive SCI; and (2) the effects of exogenous PLA2 on spinal cord neuronal death in vitro and tissue damage, inflammation, and function in vivo. Results After SCI, both PLA2 activity and cytosolic PLA2 expression increased significantly, with cytosolic PLA2 expression being localized mainly in neurons and oligodendrocytes. Both PLA2 and melittin, an activator of endogenous PLA2, induced spinal neuronal death in vitro, which was substantially reversed by mepacrine, a PLA2 inhibitor. When PLA2 or melittin was microinjected into the normal spinal cord, the former induced confined demyelination and latter diffuse tissue necrosis. Both injections induced inflammation, oxidation, and tissue damage, resulting in corresponding electrophysiological and behavioral impairments. Importantly, the PLA2-induced demyelination was significantly reversed by mepacrine. Interpretation PLA2, increased significantly after SCI, may play a key role in mediating neuronal death and oligodendrocyte demyelination following SCI. Blocking PLA2 action may represent a novel repair strategy to reduce tissue damage and increase function after SCI. Ann Neurol 2006

Annexin A1 Reduces Inflammatory Reaction and Tissue Damage Through Inhibition of Phospholipase A2 Activation in Adult Rats Following Spinal Cord Injury

Abstract: Annexin A1 (ANXA1) has been suggested to be a mediator of the anti-inflammatory actions of glucocorticoids and more recently an endogenous neuroprotective agent. In the present study, we investigated the anti-inflammatory and neuroprotective effects of ANXA1 in a model of contusive spinal cord injury (SCI). Here we report that injections of ANXA1 (Ac 2-26) into the acutely injured spinal cord at 2 concentrations (5 and 20 μg) inhibited SCI-induced increases in phospholipase A2 and myeloperoxidase activities. In addition, ANXA1 administration reduced the expression of interleukin-1β and activated caspase-3 at 24 hours, and glial fibrillary acidic protein at 4 weeks postinjury. Furthermore, ANXA1 administration significantly reversed phospholipase A2-induced spinal cord neuronal death in vitro and reduced tissue damage and increased white matter sparing in vivo, compared to the vehicle-treated controls. Fluorogold retrograde tracing showed that ANXA1 administration protected axons of long descending pathways at 6 weeks post-SCI. ANXA1 administration also significantly increased the number of animals that responded to transcranial magnetic motor-evoked potentials. However, no measurable behavioral improvement was found after these treatments. These results, particularly the improvements obtained in tissue sparing and electrophysiologic measures, suggest a neuroprotective effect of ANXA1.

Upregulation of annexins I, II, and V after traumatic spinal cord injury in adult rats.

Abstract: The posttraumatic inflammatory reaction contributes to progressive tissue damage after spinal cord injury (SCI). Annexins, a family of structurally related calcium- and phospholipid-binding proteins, have potent anti-inflammatory effects by inhibiting the activity of phospholipase A(2) (PLA(2)), a key enzyme responsible for inflammation and cytotoxicity. We investigated spatiotemporal expression of annexins I, II, and V after a contusive SCI using the New York University impact device (a 10-g rod, height 12.5 mm) in adult rats. Western blot analysis revealed that annexin I expression increased at 3 days after injury, peaked at 7 days (1.75-fold above the baseline level; P < 0.01), started to decline at 14 days, and returned to the baseline level at and beyond 28 days post-injury. The expression of annexin II started to increase at 3 days, reached its maximal level at 14 days (2.73-fold; P < 0.01), remained at a high level up to 28 days, and then declined to the basal level by 56 days after injury. Annexin V expression started at 3 days, reached its maximal level at 7 days (1.61-fold; P < 0.05) and remained at this level until 56 days after injury. RT-PCR results confirmed expression of all three annexins at the mRNA level after SCI. Immunohistochemistry and immunofluorescence double-labeling analyses revealed that increased annexins I, II, and V were localized in neurons and glial cells. The present study thus revealed increased expression of the three annexin isoforms after moderate contusive SCI. The precise role of annexins in posttraumatic inflammation and neuroprotection after SCI remains to be determined.

Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities.

Abstract: Reactive oxygen species (ROS) are produced at low levels in mammalian cells by various metabolic processes, such as oxidative phosphorylation by the mitochondrial respiratory chain, NAD(P)H oxidases, and arachidonic acid oxidative metabolism. To maintain physiological redox balance, cells have endogenous antioxidant defenses regulated at the transcriptional level by Nrf2/ARE. Oxidative stress results when ROS production exceeds the cell's ability to detoxify ROS. Overproduction of ROS damages cellular components, including lipids, leading to decline in physiological function and cell death. Reaction of ROS with lipids produces oxidized phospholipids, which give rise to 4-hydroxynonenal, 4-oxo-2-nonenal, and acrolein. The brain is susceptible to oxidative damage due to its high lipid content and oxygen consumption. Neurodegenerative diseases (AD, ALS, bipolar disorder, epilepsy, Friedreich's ataxia, HD, MS, NBIA, NPC, PD, peroxisomal disorders, schizophrenia, Wallerian degeneration, Zellweger syndrome) and CNS traumas (stroke, TBI, SCI) are problems of vast clinical importance. Free iron can react with H(2)O(2) via the Fenton reaction, a primary cause of lipid peroxidation, and may be of particular importance for these CNS injuries and disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Atherosclerosis, the major risk factor for ischemic stroke, involves accumulation of oxidized LDL in the arteries, leading to foam cell formation and plaque development. This review will discuss the role of lipid oxidation/peroxidation in various CNS injuries/disorders.

Degenerative and spontaneous regenerative processes after spinal cord injury.

Abstract: Spinal cord injury results in acute as well as progressive secondary destruction of local and distant nervous tissue through a number of degenerative mechanisms. Spinal cord injury also initiates a number of endogenous neuroprotective and regenerative responses. Understanding of these mechanisms might identify potential targets for treatments after spinal cord injury in humans. Here, we first discuss recent developments in our understanding of the immediate traumatic and subsequent secondary degeneration of local tissue and long projecting pathways in animal models. These include the inflammatory and vascular responses during the acute phase, as well as cell death, demyelination and scar formation in the subacute and chronic phases. Secondly, we discuss the spontaneous axonal regeneration of injured and plasticity of uninjured systems, and other repair-related responses in animals, including the upregulation of regeneration-associated genes in some neurons, increases in neurotrophic factors in the spinal cord and remyelination by oligodendrocyte precursors and invading Schwann cells. Lastly, we comment on the still limited understanding of the neuropathology in humans, which is largely similar to that in rodents. However, there also are potentially important differences, including the reduced glial scarring, inflammation and demyelination, the increased Schwannosis and the protracted Wallerian degeneration in humans. The validity of current rodent models for human spinal cord injury is also discussed. The emphasis of this review is on the literature from 2002 to early 2005.