Yolanda Cruz | Universidad Anahuac (original) (raw)

Papers by Yolanda Cruz

Research paper thumbnail of Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Neuroscience Letters, 2013

Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In a... more Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In an attempt to establish a preventive therapy for anticipated SC injury, we tested the effect of a single dose (SD) vaccine vs. the addition of a booster dose (BD) of a neural-derived peptide (A91) prior to SC contusion. Immunization with A91 immediately after SC injury has demonstrated to induce significant tissue protection and motor recovery. After injury, only the BD vaccination schedule had a neuroprotective effect. It was capable of improving neurological recovery that was always significantly higher than the one observed in rats with SD immunization or those only treated with PBS. Toward the end of study, animals treated with an A91 BD presented a BBB score of 9.75 ± 0.17 (mean ± standard deviation) while rats treated with SD or PBS had a score of 6.6 ± 0.7 and 5.6 ± 0.6 respectively. In the next step we attempted to corroborate the neuroprotective effect induced by A91 immunization. For this purpose, we assessed the survival of rubrospinal neurons (RSNs) and ventral horn neurons (VHNs) sixty days after SC injury. BD vaccination induced a significant survival of both RSNs and VHNs after injury. Finally, the failure or success of this therapy (SD or BD respectively) was associated with a lower (SD) or higher (BD) A91-specific T cell proliferation. Prophylactic neuroprotection with an initial and subsequent booster dose of A91 may improve recovery after SC injury sustained during invasive spinal surgery procedures.

Research paper thumbnail of Release of interleukin-10 and neurotrophic factors in the choroid plexus: possible inductors of neurogenesis following copolymer-1 immunization after cerebral ischemia

Neural regeneration research, 2018

Copolymer-1 (Cop-1) is a peptide with immunomodulatory properties, approved by the Food and Drug ... more Copolymer-1 (Cop-1) is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus (CP) is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3) and cytokines (tumor necrosis factor alpha, interferon-gamma, interleukin-4 (IL-4), IL-10...

Research paper thumbnail of Immunization with Cop-1 promotes neuroprotection and neurogenesis after ischemic stroke

Neural Regeneration Research, 2015

Research paper thumbnail of Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

Ischemic Stroke - Updates, 2016

Cerebrovascular diseases are currently among the three primary causes of death worldwide and are ... more Cerebrovascular diseases are currently among the three primary causes of death worldwide and are the first cause of disability in adults. Nevertheless, there are no neuroprotective or neurorestorative therapies that have shown considerable beneficial effects, except for the FDA-approved recombinant tissue plasminogen activator (rtPA), which has been used for decades for the treatment of stroke and its effectiveness is still controversial. This is why it is very important to develop effective therapeutic options. In order to achieve this objective, it is essential to recognize the secondary mechanisms involved in the pathological development. The immunological system is one of these mechanisms that participate during the acute and chronic phases of disease, both in deleterious and beneficial manners. It is known that the immune system's duality contributes to the ischemic injury through proinflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6)), and oxygen reactive species production, etc. Nevertheless, it also provides protection and even restoration through anti-inflammatory cytokine (interleukin-4 (IL-4), interleukin-10 (IL-10), transforming growth factor-β (TGF-β)), and growth factor (brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)) production. This states that innovative therapeutic options must be proposed with the goal of protecting and restoring the tissue after the ischemic event. Such therapies are exposed in the present chapter.

Research paper thumbnail of Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

Ischemic Stroke - Updates, 2016

Cerebrovascular diseases are currently among the three primary causes of death worldwide and are ... more Cerebrovascular diseases are currently among the three primary causes of death worldwide and are the first cause of disability in adults. Nevertheless, there are no neuroprotective or neurorestorative therapies that have shown considerable beneficial effects, except for the FDA-approved recombinant tissue plasminogen activator (rtPA), which has been used for decades for the treatment of stroke and its effectiveness is still controversial. This is why it is very important to develop effective therapeutic options. In order to achieve this objective, it is essential to recognize the secondary mechanisms involved in the pathological development. The immunological system is one of these mechanisms that participate during the acute and chronic phases of disease, both in deleterious and beneficial manners. It is known that the immune system's duality contributes to the ischemic injury through proinflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6)), and oxygen reactive species production, etc. Nevertheless, it also provides protection and even restoration through anti-inflammatory cytokine (interleukin-4 (IL-4), interleukin-10 (IL-10), transforming growth factor-β (TGF-β)), and growth factor (brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)) production. This states that innovative therapeutic options must be proposed with the goal of protecting and restoring the tissue after the ischemic event. Such therapies are exposed in the present chapter.

Research paper thumbnail of Lewis, Fischer 344, and Sprague-Dawley Rats Display Differences in Lipid Peroxidation, Motor Recovery, and Rubrospinal Tract Preservation after Spinal Cord Injury

Frontiers in Neurology, 2015

The rat is the most common animal model for the preclinical validation of neuroprotective therapi... more The rat is the most common animal model for the preclinical validation of neuroprotective therapies in spinal cord injury (SCI). Lipid peroxidation (LP) is a hallmark of the damage triggered after SCI. Free radicals react with fatty acids causing cellular and membrane disruption. LP accounts for a considerable amount of neuronal cell death after SCI. To better understand the implications of inbred and outbred rat strain selection on preclinical SCI research, we evaluated LP after laminectomy sham surgery and a severe contusion of the T9 spinal cord in female Sprague-Dawley (SPD), Lewis (LEW), and Fischer 344 (F344) rats. Further analysis included locomotor recovery using the Basso, Beattie, and Bresnahan (BBB) scale and retrograde rubrospinal tract tracing. LEW had the highest levels of LP products 72 h after sham surgery and SCI, significantly different from both F344 and SPD. SPD rats had the fastest functional recovery and highest BBB scores; these were not significantly different to F344. However, LEW rats achieved the lowest BBB scores throughout the 2-month follow-up, yielding significant differences when compared to SPD and F344. To see if the improvement in locomotion was secondary to an increase in axon survival, we evaluated rubrospinal neurons (RSNs) via retrograde labeling of the rubrospinal tract and quantified cells at the red nuclei. The highest numbers of RSNs were observed in SPD rats then F344; the lowest counts were seen in LEW rats. The BBB scores significantly correlated with the amount of positively stained RSN in the red nuclei. It is critical to identify interstrain variations as a potential confound in preclinical research. Multi-strain validation of neuroprotective therapies may increase chances of successful translation.

Research paper thumbnail of Copolymer-1 promotes neurogenesis and improves functional recovery after acute ischemic stroke in rats

PloS one, 2015

Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing ... more Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurog...

Research paper thumbnail of Copolymer-1 (Cop-1) improves neurological recovery after middle cerebral artery occlusion in rats

Neuroscience Letters, 2007

The damage in ischemic stroke is caused by two events: (i) the ischemic phenomenon by itself; (ii... more The damage in ischemic stroke is caused by two events: (i) the ischemic phenomenon by itself; (ii) the self-destructive mechanisms developed as a consequence of ischemia. The inflammatory response is one of these destructive phenomena that accompanies and exacerbates the developing injury. Since it has been suggested that immune cells participate in neuroprotective and restorative processes, modulation rather than elimination of this inflammatory response could be a strategy to improve the neurological outcome. The immune modulator copolymer-1 (Cop-1), a synthetic basic random copolymer of amino acids, is a potent inducer of Th2 regulatory cells which, aside from exerting modulatory actions, is capable of releasing neurotrophic factors. There is evidence that Cop-1-specific T cells exert neuroprotective and even restorative effects in diverse neurodegenerative diseases. In order to test the ability of Cop-1 to prevent ischemic injury in a model of transient middle cerebral artery (MCA) occlusion, two groups of rats were treated either with Cop-1 or with saline solution (SS). Seven days after occlusion, Cop-1 treated rats presented a significant improvement in neurological function compared to SS-treated animals (1.2+/-0.4 and 2.8+/-0.5 mean+/-S.D., respectively; p=0.008). Histological findings showed that the percentage of infarct volume was smaller in Cop-1 treated rats (4.8+/-1.5), in comparison with those receiving SS (32.2+/-8.6; p=0.004). Cop-1 constitutes a promising therapy for stroke; thereby, the enforcement of further experimental investigation is encouraged in order to be able to formulate the best strategy.

Research paper thumbnail of Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Neuroscience Letters, 2013

Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In a... more Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In an attempt to establish a preventive therapy for anticipated SC injury, we tested the effect of a single dose (SD) vaccine vs. the addition of a booster dose (BD) of a neural-derived peptide (A91) prior to SC contusion. Immunization with A91 immediately after SC injury has demonstrated to induce significant tissue protection and motor recovery. After injury, only the BD vaccination schedule had a neuroprotective effect. It was capable of improving neurological recovery that was always significantly higher than the one observed in rats with SD immunization or those only treated with PBS. Toward the end of study, animals treated with an A91 BD presented a BBB score of 9.75±0.17 (mean±standard deviation) while rats treated with SD or PBS had a score of 6.6±0.7 and 5.6±0.6 respectively. In the next step we attempted to corroborate the neuroprotective effect induced by A91 immunization. For this purpose, we assessed the survival of rubrospinal neurons (RSNs) and ventral horn neurons (VHNs) sixty days after SC injury. BD vaccination induced a significant survival of both RSNs and VHNs after injury. Finally, the failure or success of this therapy (SD or BD respectively) was associated with a lower (SD) or higher (BD) A91-specific T cell proliferation. Prophylactic neuroprotection with an initial and subsequent booster dose of A91 may improve recovery after SC injury sustained during invasive spinal surgery procedures.

Research paper thumbnail of Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Neuroscience Letters, 2013

Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In a... more Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In an attempt to establish a preventive therapy for anticipated SC injury, we tested the effect of a single dose (SD) vaccine vs. the addition of a booster dose (BD) of a neural-derived peptide (A91) prior to SC contusion. Immunization with A91 immediately after SC injury has demonstrated to induce significant tissue protection and motor recovery. After injury, only the BD vaccination schedule had a neuroprotective effect. It was capable of improving neurological recovery that was always significantly higher than the one observed in rats with SD immunization or those only treated with PBS. Toward the end of study, animals treated with an A91 BD presented a BBB score of 9.75 ± 0.17 (mean ± standard deviation) while rats treated with SD or PBS had a score of 6.6 ± 0.7 and 5.6 ± 0.6 respectively. In the next step we attempted to corroborate the neuroprotective effect induced by A91 immunization. For this purpose, we assessed the survival of rubrospinal neurons (RSNs) and ventral horn neurons (VHNs) sixty days after SC injury. BD vaccination induced a significant survival of both RSNs and VHNs after injury. Finally, the failure or success of this therapy (SD or BD respectively) was associated with a lower (SD) or higher (BD) A91-specific T cell proliferation. Prophylactic neuroprotection with an initial and subsequent booster dose of A91 may improve recovery after SC injury sustained during invasive spinal surgery procedures.

Research paper thumbnail of Release of interleukin-10 and neurotrophic factors in the choroid plexus: possible inductors of neurogenesis following copolymer-1 immunization after cerebral ischemia

Neural regeneration research, 2018

Copolymer-1 (Cop-1) is a peptide with immunomodulatory properties, approved by the Food and Drug ... more Copolymer-1 (Cop-1) is a peptide with immunomodulatory properties, approved by the Food and Drug Administration of United States in the treatment of multiple sclerosis. Cop-1 has been shown to exert neuroprotective effects and induce neurogenesis in cerebral ischemia models. Nevertheless, the mechanism involved in the neurogenic action of this compound remains unknown. The choroid plexus (CP) is a network of cells that constitute the interphase between the immune and central nervous systems, with the ability to mediate neurogenesis through the release of cytokines and growth factors. Therefore, the CP could play a role in Cop-1-induced neurogenesis. In order to determine the participation of the CP in the induction of neurogenesis after Cop-1 immunization, we evaluated the gene expression of various growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1, neurotrophin-3) and cytokines (tumor necrosis factor alpha, interferon-gamma, interleukin-4 (IL-4), IL-10...

Research paper thumbnail of Immunization with Cop-1 promotes neuroprotection and neurogenesis after ischemic stroke

Neural Regeneration Research, 2015

Research paper thumbnail of Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

Ischemic Stroke - Updates, 2016

Cerebrovascular diseases are currently among the three primary causes of death worldwide and are ... more Cerebrovascular diseases are currently among the three primary causes of death worldwide and are the first cause of disability in adults. Nevertheless, there are no neuroprotective or neurorestorative therapies that have shown considerable beneficial effects, except for the FDA-approved recombinant tissue plasminogen activator (rtPA), which has been used for decades for the treatment of stroke and its effectiveness is still controversial. This is why it is very important to develop effective therapeutic options. In order to achieve this objective, it is essential to recognize the secondary mechanisms involved in the pathological development. The immunological system is one of these mechanisms that participate during the acute and chronic phases of disease, both in deleterious and beneficial manners. It is known that the immune system's duality contributes to the ischemic injury through proinflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6)), and oxygen reactive species production, etc. Nevertheless, it also provides protection and even restoration through anti-inflammatory cytokine (interleukin-4 (IL-4), interleukin-10 (IL-10), transforming growth factor-β (TGF-β)), and growth factor (brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)) production. This states that innovative therapeutic options must be proposed with the goal of protecting and restoring the tissue after the ischemic event. Such therapies are exposed in the present chapter.

Research paper thumbnail of Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke

Ischemic Stroke - Updates, 2016

Cerebrovascular diseases are currently among the three primary causes of death worldwide and are ... more Cerebrovascular diseases are currently among the three primary causes of death worldwide and are the first cause of disability in adults. Nevertheless, there are no neuroprotective or neurorestorative therapies that have shown considerable beneficial effects, except for the FDA-approved recombinant tissue plasminogen activator (rtPA), which has been used for decades for the treatment of stroke and its effectiveness is still controversial. This is why it is very important to develop effective therapeutic options. In order to achieve this objective, it is essential to recognize the secondary mechanisms involved in the pathological development. The immunological system is one of these mechanisms that participate during the acute and chronic phases of disease, both in deleterious and beneficial manners. It is known that the immune system's duality contributes to the ischemic injury through proinflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6)), and oxygen reactive species production, etc. Nevertheless, it also provides protection and even restoration through anti-inflammatory cytokine (interleukin-4 (IL-4), interleukin-10 (IL-10), transforming growth factor-β (TGF-β)), and growth factor (brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)) production. This states that innovative therapeutic options must be proposed with the goal of protecting and restoring the tissue after the ischemic event. Such therapies are exposed in the present chapter.

Research paper thumbnail of Lewis, Fischer 344, and Sprague-Dawley Rats Display Differences in Lipid Peroxidation, Motor Recovery, and Rubrospinal Tract Preservation after Spinal Cord Injury

Frontiers in Neurology, 2015

The rat is the most common animal model for the preclinical validation of neuroprotective therapi... more The rat is the most common animal model for the preclinical validation of neuroprotective therapies in spinal cord injury (SCI). Lipid peroxidation (LP) is a hallmark of the damage triggered after SCI. Free radicals react with fatty acids causing cellular and membrane disruption. LP accounts for a considerable amount of neuronal cell death after SCI. To better understand the implications of inbred and outbred rat strain selection on preclinical SCI research, we evaluated LP after laminectomy sham surgery and a severe contusion of the T9 spinal cord in female Sprague-Dawley (SPD), Lewis (LEW), and Fischer 344 (F344) rats. Further analysis included locomotor recovery using the Basso, Beattie, and Bresnahan (BBB) scale and retrograde rubrospinal tract tracing. LEW had the highest levels of LP products 72 h after sham surgery and SCI, significantly different from both F344 and SPD. SPD rats had the fastest functional recovery and highest BBB scores; these were not significantly different to F344. However, LEW rats achieved the lowest BBB scores throughout the 2-month follow-up, yielding significant differences when compared to SPD and F344. To see if the improvement in locomotion was secondary to an increase in axon survival, we evaluated rubrospinal neurons (RSNs) via retrograde labeling of the rubrospinal tract and quantified cells at the red nuclei. The highest numbers of RSNs were observed in SPD rats then F344; the lowest counts were seen in LEW rats. The BBB scores significantly correlated with the amount of positively stained RSN in the red nuclei. It is critical to identify interstrain variations as a potential confound in preclinical research. Multi-strain validation of neuroprotective therapies may increase chances of successful translation.

Research paper thumbnail of Copolymer-1 promotes neurogenesis and improves functional recovery after acute ischemic stroke in rats

PloS one, 2015

Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing ... more Stroke triggers a systemic inflammatory response that exacerbates the initial injury. Immunizing with peptides derived from CNS proteins can stimulate protective autoimmunity (PA). The most renowned of these peptides is copolymer-1 (Cop-1) also known as glatiramer acetate. This peptide has been approved for use in the treatment of multiple sclerosis. Cop-1-specific T cells cross the blood-brain barrier and secrete neurotrophins and anti-inflammatory cytokines that could stimulate proliferation of neural precursor cells and recruit them to the injury site; making it an ideal therapy for acute ischemic stroke. The aim of this work was to evaluate the effect of Cop-1 on neurogenesis and neurological recovery during the acute phase (7 days) and the chronic phase of stroke (60 days) in a rat model of transient middle cerebral artery occlusion (tMCAo). BDNF and NT-3 were quantified and infarct volumes were measured. We demonstrated that Cop-1 improves neurological deficit, enhances neurog...

Research paper thumbnail of Copolymer-1 (Cop-1) improves neurological recovery after middle cerebral artery occlusion in rats

Neuroscience Letters, 2007

The damage in ischemic stroke is caused by two events: (i) the ischemic phenomenon by itself; (ii... more The damage in ischemic stroke is caused by two events: (i) the ischemic phenomenon by itself; (ii) the self-destructive mechanisms developed as a consequence of ischemia. The inflammatory response is one of these destructive phenomena that accompanies and exacerbates the developing injury. Since it has been suggested that immune cells participate in neuroprotective and restorative processes, modulation rather than elimination of this inflammatory response could be a strategy to improve the neurological outcome. The immune modulator copolymer-1 (Cop-1), a synthetic basic random copolymer of amino acids, is a potent inducer of Th2 regulatory cells which, aside from exerting modulatory actions, is capable of releasing neurotrophic factors. There is evidence that Cop-1-specific T cells exert neuroprotective and even restorative effects in diverse neurodegenerative diseases. In order to test the ability of Cop-1 to prevent ischemic injury in a model of transient middle cerebral artery (MCA) occlusion, two groups of rats were treated either with Cop-1 or with saline solution (SS). Seven days after occlusion, Cop-1 treated rats presented a significant improvement in neurological function compared to SS-treated animals (1.2+/-0.4 and 2.8+/-0.5 mean+/-S.D., respectively; p=0.008). Histological findings showed that the percentage of infarct volume was smaller in Cop-1 treated rats (4.8+/-1.5), in comparison with those receiving SS (32.2+/-8.6; p=0.004). Cop-1 constitutes a promising therapy for stroke; thereby, the enforcement of further experimental investigation is encouraged in order to be able to formulate the best strategy.

Research paper thumbnail of Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Neuroscience Letters, 2013

Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In a... more Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In an attempt to establish a preventive therapy for anticipated SC injury, we tested the effect of a single dose (SD) vaccine vs. the addition of a booster dose (BD) of a neural-derived peptide (A91) prior to SC contusion. Immunization with A91 immediately after SC injury has demonstrated to induce significant tissue protection and motor recovery. After injury, only the BD vaccination schedule had a neuroprotective effect. It was capable of improving neurological recovery that was always significantly higher than the one observed in rats with SD immunization or those only treated with PBS. Toward the end of study, animals treated with an A91 BD presented a BBB score of 9.75±0.17 (mean±standard deviation) while rats treated with SD or PBS had a score of 6.6±0.7 and 5.6±0.6 respectively. In the next step we attempted to corroborate the neuroprotective effect induced by A91 immunization. For this purpose, we assessed the survival of rubrospinal neurons (RSNs) and ventral horn neurons (VHNs) sixty days after SC injury. BD vaccination induced a significant survival of both RSNs and VHNs after injury. Finally, the failure or success of this therapy (SD or BD respectively) was associated with a lower (SD) or higher (BD) A91-specific T cell proliferation. Prophylactic neuroprotection with an initial and subsequent booster dose of A91 may improve recovery after SC injury sustained during invasive spinal surgery procedures.