Table 2.

Preclinical studies of human platelet lysate and extracellular vesicle preparations for the treatment of neurological diseases

MaterialDiseasePlatelet preparation, model, and administration routeBiological effectsReferences
HPL Stroke PMCAO Intracerebroventricular NSC proliferation and angiogenesis Improved cognition 49  
 AD Primary cortical and hippocampal neurons APP/PS1 mouse model; intranasal delivery Proliferation and survival of primary neurons Hippocampal neurogenesis and reduced Aβ-induced neurodegeneration 121  
 PD Human dopaminergic neuroblastoma cell line (SH-SY5Y) treated with MPP+MPTP mouse model; intranasal administration Protection against MPP+ toxicity Diminished inflammatory responses Improved motor performance 122  
  LUHMES cells exposed to MPP+MPTP mouse model; intranasal administration In vitro and in vivo protection of dopaminergic neurons 119  
  LUHMES cells exposed to prooxidants and regulated cell death inducers Strong neuroprotection through activation of the Akt and MEK pathways 123  
  LUHMES cells; primary cortical and hippocampal neurons Enhanced expression of tyrosine hydroxylase and neuron-specific enolase in LUHMES cells and strong protection against ferroptosis 117  
 BI and TBI Proliferating SEZ-derived NPCs Increased proliferating SEZ-derived NPCs maintaining proliferative or lineage-differentiation capacity 46  
  Undifferentiated SH-SY5Y neuroblastoma cells; Ea-hy926 human endothelial cell; BV2 microglial cells No toxicity and no inflammation Stimulation of wound healing and neuronal differentiation of SH-SY5Y 125  
  Scratch assay (differentiated SH-SY5Y cells) Mouse models of TBI; topical followed by daily intranasal administration Wound healing Improved motor function; mitigation of cortical neuroinflammation and oxidative stress in the injured area; reduced loss of cortical synaptic proteins 40  
 ALS NSC34 motoneurons exposed to various neurotoxins Strong neuroprotection through activation of the Akt and MEK pathways 123  
  Motoneuron cultures SOD1G86R; intracerebroventricular or intranasal administration Akt-dependent neuroprotection, antiapoptotic and antiferroptotic actions Increased lifespan 126  
EVs Stroke PMCAO in vivo model; topical application by biodegradable polymer Neurogenesis and angiogenesis Improved behavioral function 48  
 BI and TBI In vitro assay of NSC proliferation, survival, and differentiation Increased proliferation, survival, and differentiation, through ERK and Akt signaling 47  
  Wound healing (SH-SY5Y) Mouse primary neuronal cells Nontoxicity Promotion of cell growth and migration Stimulation of network formation in primary neuronal cultures 130  
MaterialDiseasePlatelet preparation, model, and administration routeBiological effectsReferences
HPL Stroke PMCAO Intracerebroventricular NSC proliferation and angiogenesis Improved cognition 49  
 AD Primary cortical and hippocampal neurons APP/PS1 mouse model; intranasal delivery Proliferation and survival of primary neurons Hippocampal neurogenesis and reduced Aβ-induced neurodegeneration 121  
 PD Human dopaminergic neuroblastoma cell line (SH-SY5Y) treated with MPP+MPTP mouse model; intranasal administration Protection against MPP+ toxicity Diminished inflammatory responses Improved motor performance 122  
  LUHMES cells exposed to MPP+MPTP mouse model; intranasal administration In vitro and in vivo protection of dopaminergic neurons 119  
  LUHMES cells exposed to prooxidants and regulated cell death inducers Strong neuroprotection through activation of the Akt and MEK pathways 123  
  LUHMES cells; primary cortical and hippocampal neurons Enhanced expression of tyrosine hydroxylase and neuron-specific enolase in LUHMES cells and strong protection against ferroptosis 117  
 BI and TBI Proliferating SEZ-derived NPCs Increased proliferating SEZ-derived NPCs maintaining proliferative or lineage-differentiation capacity 46  
  Undifferentiated SH-SY5Y neuroblastoma cells; Ea-hy926 human endothelial cell; BV2 microglial cells No toxicity and no inflammation Stimulation of wound healing and neuronal differentiation of SH-SY5Y 125  
  Scratch assay (differentiated SH-SY5Y cells) Mouse models of TBI; topical followed by daily intranasal administration Wound healing Improved motor function; mitigation of cortical neuroinflammation and oxidative stress in the injured area; reduced loss of cortical synaptic proteins 40  
 ALS NSC34 motoneurons exposed to various neurotoxins Strong neuroprotection through activation of the Akt and MEK pathways 123  
  Motoneuron cultures SOD1G86R; intracerebroventricular or intranasal administration Akt-dependent neuroprotection, antiapoptotic and antiferroptotic actions Increased lifespan 126  
EVs Stroke PMCAO in vivo model; topical application by biodegradable polymer Neurogenesis and angiogenesis Improved behavioral function 48  
 BI and TBI In vitro assay of NSC proliferation, survival, and differentiation Increased proliferation, survival, and differentiation, through ERK and Akt signaling 47  
  Wound healing (SH-SY5Y) Mouse primary neuronal cells Nontoxicity Promotion of cell growth and migration Stimulation of network formation in primary neuronal cultures 130  

BI, brain injury; NSC, neural stem cell; PMCAO, permanent distal middle cerebral artery occlusion; SEZ, subependymal zone.

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